<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01700335</url>
  </required_header>
  <id_info>
    <org_study_id>2011005</org_study_id>
    <nct_id>NCT01700335</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetics Study of SyB L-1101 in Patients With Recurrent/Relapsed or Refractory Myelodysplastic Syndrome (MDS)</brief_title>
  <official_title>Phase I Clinical Trial of SyB L-1101 in Patients With Myelodysplastic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SymBio Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SymBio Pharmaceuticals</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate tolerability when SyB L-1101 is administered&#xD;
      intravenously in patients with recurrent/relapsed or refractory myelodysplastic syndrome, to&#xD;
      determine the dose-limiting toxicity and maximum tolerated dose, and to estimate the&#xD;
      recommended dose for phase II studies. Pharmacokinetics and antitumor effects will also be&#xD;
      investigated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)</measure>
    <time_frame>Up to 60 weeks</time_frame>
    <description>A DLT was defined as adverse events for which a causal relationship with the investigational drug could not be ruled out and which met the following criteria that occurred by the final observation in Cycle 2. DLTs were also to be assessed in the Efficacy and Safety Assessment Committee.&#xD;
Criteria:&#xD;
Grade 3 or higher non-hematologic toxicity. However, nausea, vomiting, diarrhea, pyrexia, stomatitis, and esophagitis/dysphagia are excluded (Grade 3 nausea, vomiting, diarrhea, and pyrexia that cannot be controlled with antiemetic, antidiarrheal, or antifebrile agents are regarded as DLTs)&#xD;
Grade 3 or higher stomatitis, esophagitis, and dysphagia that persist for &gt;= 4 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hematologic Remission Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 4 Weeks)</measure>
    <time_frame>Up to 60 weeks</time_frame>
    <description>Definition&#xD;
Complete remission (CR) Bone marrow: &lt;= 5% myeloblasts; normal maturation of all cell lines Peripheral blood: Hemoglobin (Hgb) &gt;= 11 g/dL, Platelets &gt;= 100×10^9/L, Neutrophils &gt;= 1.0×10^9/L, Blasts 0%&#xD;
Partial remission (PR) Same as CR criteria except bone marrow blasts decreased by &gt;= 50% over pretreatment but still &gt; 5%&#xD;
Marrow CR Bone marrow: &lt;= 5% myeloblasts and decrease by &gt;= 50% over pretreatment Peripheral blood: will be noted in addition to marrow CR&#xD;
Stable disease Failure to achieve at least PR, but no evidence of progression for &gt; 8 wks&#xD;
Disease progression&#xD;
Patients with:&#xD;
Less than 5% blasts: &gt;= 50% increase in blasts to &gt; 5% blasts 5%-10% blasts: &gt;= 50% increase to &gt; 10% blasts 10%-20% blasts: &gt;= 50% increase to &gt; 20% blasts 20%-30% blasts: &gt;= 50% increase to &gt; 30% blasts&#xD;
Any of the following:&#xD;
At least 50% decrement from maximum remission/response in granulocytes or platelets Reduction in Hgb by &gt;= 2 g/dL Transfusion dependence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic Improvement Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 8 Weeks)</measure>
    <time_frame>Up to 60 weeks</time_frame>
    <description>Definition&#xD;
Hematologic Improvement Erythrocyte (HI-E):&#xD;
Hgb increase by &gt;= 1.5 g/dL Relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. Only RBC transfusions given for a Hgb of &lt;= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation&#xD;
Hematologic Improvement Platelet (HI-P):&#xD;
Absolute increase of &gt;= 30×10^9/L for patients starting with &gt; 20×10^9/L platelets Increase from &lt; 20×10^9/L to &gt; 20×10^9/L and by at least 100%&#xD;
Hematologic Improvement Neutrophil (HI-N):&#xD;
At least 100% increase and an absolute increase &gt; 0.5×10^9/L&#xD;
Progressive disease / Relapse:&#xD;
At least 1 of the following:&#xD;
At least 50% decrement from maximum response levels in granulocytes or platelets Reduction in Hgb by &gt;= 1.5 g/dL Transfusion dependence</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Up to 16 weeks</time_frame>
    <description>MTD was investigated with an index of DLT</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Myelodysplastic Syndrome</condition>
  <arm_group>
    <arm_group_label>SyB L-1101</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Cohort 1, SyB L-1101 1200 mg/day group, Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
In Cohort 2, SyB L-1101 1800 mg/day group, Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
For both Cohorts, the treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SyB L-1101</intervention_name>
    <description>SyB L-1101（rigosertib sodium） will be administered to two cohorts at either 1200 mg/day or 1800 mg/day.&#xD;
The dose will be administered intravenously for 72 continuous hours (3 days), followed by 11-day observation period. The treatment period of 14 days (3 days of administration + 11 days of observation) constitutes 1 cycle.&#xD;
The study will involve treatment through the second cycle, but treatment can be continued for 3 or more cycles if conditions for continued administration are satisfied.</description>
    <arm_group_label>SyB L-1101</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Patients must satisfy the following conditions listed below.&#xD;
&#xD;
          1. Patients who have been histologically documented or cytologically confirmed with&#xD;
             myelodysplastic syndrome (MDS), and who have been found to meet any of the following&#xD;
             criteria on the basis of the World Health Organization (WHO) classification or&#xD;
             French-American-British (FAB) classification.&#xD;
&#xD;
               -  Refractory Anemia (RA) (&lt; 5% myeloblasts, &lt; 15% ringed sideroblasts)&#xD;
&#xD;
               -  RA with Ring Sideroblasts (RARS) (&lt; 5% myeloblasts, &gt;= 15% ringed sideroblasts)&#xD;
&#xD;
               -  RA with Excess of Blasts (RAEB)-1 (5% to 9% myeloblasts)&#xD;
&#xD;
               -  RAEB-2 (10% to 19% myeloblasts)&#xD;
&#xD;
               -  RAEB in transformation (RAEB-t) (20% to 29% myeloblasts or &lt; 25,000/mm^3&#xD;
                  peripheral leukocytes)&#xD;
&#xD;
               -  Chronic myelomonocytic leukemia (CMML) (10% to 19% myeloblasts in marrow, &gt;=&#xD;
                  1,000/mm^3 peripheral monocytes, &lt; 13,000/mm^3 leukocytes) However, RA patients&#xD;
                  must have score of Int-2 or higher in International prognostic scoring system&#xD;
                  (IPSS).&#xD;
&#xD;
          2. Patients with a low value in at least one blood cell lineage (having at least one of&#xD;
             the following cytopenias).&#xD;
&#xD;
               -  Neutrophils : &lt; 1,800/mm^3&#xD;
&#xD;
               -  Platelets : &lt; 100,000/mm^3&#xD;
&#xD;
               -  Hemoglobin : &lt; 10 g/dL&#xD;
&#xD;
          3. Patients with a previous history of chemotherapy (including lenalidomide) for the&#xD;
             target disease who meet any of the following criteria.&#xD;
&#xD;
               -  Patients who have not achieved complete remission, partial remission, or&#xD;
                  hematologic improvement*&#xD;
&#xD;
               -  Patients with recurrence/relapse after complete remission, partial remission, or&#xD;
                  hematologic improvement*&#xD;
&#xD;
               -  Patients with intolerability that has led to discontinuation of treatment because&#xD;
                  of the development of liver dysfunction, kidney dysfunction, etc., after the&#xD;
                  start of treatment. * Proximate therapeutic efficacy judged under International&#xD;
                  Working Group (IWG) 2006 criteria&#xD;
&#xD;
          4. Patients who have not been treated for four weeks or longer after the end of the&#xD;
             previous therapy and who are judged to have no residual effects (antitumor effects)&#xD;
             from the previous therapy.&#xD;
&#xD;
          5. Patients who can be expected to survive at least three months or longer.&#xD;
&#xD;
          6. Patients at least 20 years old (when informed consent is obtained).&#xD;
&#xD;
          7. Patients who have score of 0 to 2 in Eastern Cooperative Oncology Group (ECOG)&#xD;
             Performance Status (P.S.).&#xD;
&#xD;
          8. Patients with adequate function in major organs (heart, lungs, liver, kidneys, etc.).&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) (Glutamic oxaloacetic transaminase, GOT) : no&#xD;
                  greater than 3.0 times the upper boundary of the reference range at each&#xD;
                  institution&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) (Glutamic pyruvic transaminase, GPT): no greater&#xD;
                  than 3.0 times the upper boundary of the reference range at each institution&#xD;
&#xD;
               -  Total bilirubin: no more than 1.5 times the upper boundary of the reference range&#xD;
                  at each institution&#xD;
&#xD;
               -  Serum creatinine: no more than 1.5 times the upper boundary of the reference&#xD;
                  range at each institution&#xD;
&#xD;
               -  ECG: no abnormal findings requiring treatment&#xD;
&#xD;
               -  Echocardiography: no abnormal findings requiring treatment&#xD;
&#xD;
          9. Patients who personally signed an informed consent document for participation in this&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Patients who satisfy any of the following conditions will not be enrolled in the study.&#xD;
&#xD;
          1. Patients with anemia caused by factors other than MDS (hemolytic anemia,&#xD;
             gastrointestinal (GI) bleeding, etc.).&#xD;
&#xD;
          2. Patients who have undergone treatment for an active malignant tumor within the past&#xD;
             year (except basal cell or squamous cell skin cancer or carcinoma in situ of the&#xD;
             cervix or breast).&#xD;
&#xD;
          3. Patients who have been administered a cytokine preparation such as granulocyte-colony&#xD;
             stimulating factor (G-CSF), erythropoietin, etc. within 14 days of tests for&#xD;
             enrollment of the study.&#xD;
&#xD;
          4. Patients with obvious infectious diseases (including viral infections).&#xD;
&#xD;
          5. Patients with serious complications (liver failure, renal failure, etc.).&#xD;
&#xD;
          6. Patients with a complicating or previous history of serious heart disease (myocardial&#xD;
             infarction, ischemic heart disease, etc.) within the past two years before enrollment,&#xD;
             and with cardiac arrhythmia requiring treatment.&#xD;
&#xD;
          7. Patients with a serious gastrointestinal condition (severe or significant&#xD;
             nausea/vomiting, diarrhea, etc.).&#xD;
&#xD;
          8. Patients who are positive for the Hepatitis B surface (HBs) antigen or HIV antibodies.&#xD;
&#xD;
          9. Patients with serious bleeding tendencies (disseminated intravascular coagulation&#xD;
             (DIC), internal hemorrhage, etc.).&#xD;
&#xD;
         10. Ascites requiring active medical management including paracentesis, or hyponatremia&#xD;
             (defined as serum sodium value of &lt;130 mEq/L).&#xD;
&#xD;
         11. Patients who have been administered a drug in a clinical trial or an unapproved drug&#xD;
             within three months before enrollment.&#xD;
&#xD;
         12. Patients with an addiction to a legal or illegal drug, or with alcohol dependency.&#xD;
&#xD;
         13. Patients who are pregnant or may become pregnant.&#xD;
&#xD;
         14. Patients who have not consented to the following contraceptive measures.&#xD;
&#xD;
             Patients will avoid sexual intercourse with sexual partners or should use the&#xD;
             following contraceptive methods in these time periods: for male patients during the&#xD;
             administration period of the trial and for six months after the end of administration;&#xD;
             female patients during the administration period of the trial, and until a second&#xD;
             menstrual period is confirmed after the end of administration (or in the case of&#xD;
             female patients with no menstrual period, for two months after the end of&#xD;
             administration).&#xD;
&#xD;
             •Male patients&#xD;
&#xD;
             The patient will always use a condom. For effective contraception, it is recommended&#xD;
             that the female partner also use the contraceptive methods for female patients.&#xD;
&#xD;
             •Female patients&#xD;
&#xD;
             Female patients who may become pregnant should use one or more types of the following&#xD;
             contraceptive methods. In addition, the male partner will always use a condom.&#xD;
&#xD;
               -  Oral contraceptive (birth control pills)&#xD;
&#xD;
               -  Intrauterine device (IUD)&#xD;
&#xD;
               -  Tubal ligation&#xD;
&#xD;
         15. Other patients judged to be unsuitable by an investigator or sub-investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fukuoka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <results_first_submitted>July 26, 2016</results_first_submitted>
  <results_first_submitted_qc>July 26, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 14, 2016</results_first_posted>
  <last_update_submitted>November 14, 2022</last_update_submitted>
  <last_update_submitted_qc>November 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>SyB L-1101 1200 mg/Day Group</title>
          <description>Cohort 1: Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
        </group>
        <group group_id="P2">
          <title>SyB L-1101 1800 mg/Day Group</title>
          <description>Cohort 2: Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>All participants who received at least 1 dose of SyB L-1101 either at 1200 mg/day or 1800 mg/day intravenously.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>60-69 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>80- years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)</title>
        <description>A DLT was defined as adverse events for which a causal relationship with the investigational drug could not be ruled out and which met the following criteria that occurred by the final observation in Cycle 2. DLTs were also to be assessed in the Efficacy and Safety Assessment Committee.&#xD;
Criteria:&#xD;
Grade 3 or higher non-hematologic toxicity. However, nausea, vomiting, diarrhea, pyrexia, stomatitis, and esophagitis/dysphagia are excluded (Grade 3 nausea, vomiting, diarrhea, and pyrexia that cannot be controlled with antiemetic, antidiarrheal, or antifebrile agents are regarded as DLTs)&#xD;
Grade 3 or higher stomatitis, esophagitis, and dysphagia that persist for &gt;= 4 days</description>
        <time_frame>Up to 60 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SyB L-1101 1200 mg/Day Group</title>
            <description>Cohort 1: Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
          </group>
          <group group_id="O2">
            <title>SyB L-1101 1800 mg/Day Group</title>
            <description>Cohort 2: Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)</title>
          <description>A DLT was defined as adverse events for which a causal relationship with the investigational drug could not be ruled out and which met the following criteria that occurred by the final observation in Cycle 2. DLTs were also to be assessed in the Efficacy and Safety Assessment Committee.&#xD;
Criteria:&#xD;
Grade 3 or higher non-hematologic toxicity. However, nausea, vomiting, diarrhea, pyrexia, stomatitis, and esophagitis/dysphagia are excluded (Grade 3 nausea, vomiting, diarrhea, and pyrexia that cannot be controlled with antiemetic, antidiarrheal, or antifebrile agents are regarded as DLTs)&#xD;
Grade 3 or higher stomatitis, esophagitis, and dysphagia that persist for &gt;= 4 days</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hematologic Remission Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 4 Weeks)</title>
        <description>Definition&#xD;
Complete remission (CR) Bone marrow: &lt;= 5% myeloblasts; normal maturation of all cell lines Peripheral blood: Hemoglobin (Hgb) &gt;= 11 g/dL, Platelets &gt;= 100×10^9/L, Neutrophils &gt;= 1.0×10^9/L, Blasts 0%&#xD;
Partial remission (PR) Same as CR criteria except bone marrow blasts decreased by &gt;= 50% over pretreatment but still &gt; 5%&#xD;
Marrow CR Bone marrow: &lt;= 5% myeloblasts and decrease by &gt;= 50% over pretreatment Peripheral blood: will be noted in addition to marrow CR&#xD;
Stable disease Failure to achieve at least PR, but no evidence of progression for &gt; 8 wks&#xD;
Disease progression&#xD;
Patients with:&#xD;
Less than 5% blasts: &gt;= 50% increase in blasts to &gt; 5% blasts 5%-10% blasts: &gt;= 50% increase to &gt; 10% blasts 10%-20% blasts: &gt;= 50% increase to &gt; 20% blasts 20%-30% blasts: &gt;= 50% increase to &gt; 30% blasts&#xD;
Any of the following:&#xD;
At least 50% decrement from maximum remission/response in granulocytes or platelets Reduction in Hgb by &gt;= 2 g/dL Transfusion dependence</description>
        <time_frame>Up to 60 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SyB L-1101 1200 mg/Day Group</title>
            <description>Cohort 1: Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
          </group>
          <group group_id="O2">
            <title>SyB L-1101 1800 mg/Day Group</title>
            <description>Cohort 2: Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Hematologic Remission Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 4 Weeks)</title>
          <description>Definition&#xD;
Complete remission (CR) Bone marrow: &lt;= 5% myeloblasts; normal maturation of all cell lines Peripheral blood: Hemoglobin (Hgb) &gt;= 11 g/dL, Platelets &gt;= 100×10^9/L, Neutrophils &gt;= 1.0×10^9/L, Blasts 0%&#xD;
Partial remission (PR) Same as CR criteria except bone marrow blasts decreased by &gt;= 50% over pretreatment but still &gt; 5%&#xD;
Marrow CR Bone marrow: &lt;= 5% myeloblasts and decrease by &gt;= 50% over pretreatment Peripheral blood: will be noted in addition to marrow CR&#xD;
Stable disease Failure to achieve at least PR, but no evidence of progression for &gt; 8 wks&#xD;
Disease progression&#xD;
Patients with:&#xD;
Less than 5% blasts: &gt;= 50% increase in blasts to &gt; 5% blasts 5%-10% blasts: &gt;= 50% increase to &gt; 10% blasts 10%-20% blasts: &gt;= 50% increase to &gt; 20% blasts 20%-30% blasts: &gt;= 50% increase to &gt; 30% blasts&#xD;
Any of the following:&#xD;
At least 50% decrement from maximum remission/response in granulocytes or platelets Reduction in Hgb by &gt;= 2 g/dL Transfusion dependence</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Marrow CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable disease (SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment failure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Disease progression</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not assessable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Remission rate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hematologic Improvement Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 8 Weeks)</title>
        <description>Definition&#xD;
Hematologic Improvement Erythrocyte (HI-E):&#xD;
Hgb increase by &gt;= 1.5 g/dL Relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. Only RBC transfusions given for a Hgb of &lt;= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation&#xD;
Hematologic Improvement Platelet (HI-P):&#xD;
Absolute increase of &gt;= 30×10^9/L for patients starting with &gt; 20×10^9/L platelets Increase from &lt; 20×10^9/L to &gt; 20×10^9/L and by at least 100%&#xD;
Hematologic Improvement Neutrophil (HI-N):&#xD;
At least 100% increase and an absolute increase &gt; 0.5×10^9/L&#xD;
Progressive disease / Relapse:&#xD;
At least 1 of the following:&#xD;
At least 50% decrement from maximum response levels in granulocytes or platelets Reduction in Hgb by &gt;= 1.5 g/dL Transfusion dependence</description>
        <time_frame>Up to 60 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SyB L-1101 1200 mg/Day Group</title>
            <description>Cohort 1: Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
          </group>
          <group group_id="O2">
            <title>SyB L-1101 1800 mg/Day Group</title>
            <description>Cohort 2: Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Hematologic Improvement Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 8 Weeks)</title>
          <description>Definition&#xD;
Hematologic Improvement Erythrocyte (HI-E):&#xD;
Hgb increase by &gt;= 1.5 g/dL Relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. Only RBC transfusions given for a Hgb of &lt;= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation&#xD;
Hematologic Improvement Platelet (HI-P):&#xD;
Absolute increase of &gt;= 30×10^9/L for patients starting with &gt; 20×10^9/L platelets Increase from &lt; 20×10^9/L to &gt; 20×10^9/L and by at least 100%&#xD;
Hematologic Improvement Neutrophil (HI-N):&#xD;
At least 100% increase and an absolute increase &gt; 0.5×10^9/L&#xD;
Progressive disease / Relapse:&#xD;
At least 1 of the following:&#xD;
At least 50% decrement from maximum response levels in granulocytes or platelets Reduction in Hgb by &gt;= 1.5 g/dL Transfusion dependence</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HI-E</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HI-P</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HI-N</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Relapse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not assessable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematologic improvement rate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Maximum Tolerated Dose (MTD)</title>
        <description>MTD was investigated with an index of DLT</description>
        <time_frame>Up to 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>All participants who received at least 1 dose of SyB L-1101 either at 1200 mg/day or 1800 mg/day intravenously.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD)</title>
          <description>MTD was investigated with an index of DLT</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">MTD was not reached</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 16 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SyB L-1101 1200 mg/Day Group</title>
          <description>Cohort 1: Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
        </group>
        <group group_id="E2">
          <title>SyB L-1101 1800 mg/Day Group</title>
          <description>Cohort 2: Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.&#xD;
The treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Meningitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrioventricular block second degree</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tongue haematoma</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Catheter site haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Catheter site pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Catheter site haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accident</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood calcium decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood chloride decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood uric acid decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>CD4 lymphocytes decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Protein total decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Red blood cell count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="9" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutrophil percentage decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lymphocyte percentage increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Protein urine present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hepatitis B DNA assay positive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypochloraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Laryngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>SymBio Pharmaceuticals</organization>
      <phone>+81-3-5472-1127</phone>
      <email>kgoto.34@symbiopharma.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01700335
org study id: 2011005
nct id: NCT01700335
lead sponsor: 
The purpose of this study is to investigate tolerability when SyB L-1101 is administered
      intravenously in patients with recurrent/relapsed or refractory myelodysplastic syndrome, to
      determine the dose-limiting toxicity and maximum tolerated dose, and to estimate the
      recommended dose for phase II studies. Pharmacokinetics and antitumor effects will also be
      investigated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)
time frame: Up to 60 weeks
description: A DLT was defined as adverse events for which a causal relationship with the investigational drug could not be ruled out and which met the following criteria that occurred by the final observation in Cycle 2. DLTs were also to be assessed in the Efficacy and Safety Assessment Committee.
Criteria:
Grade 3 or higher non-hematologic toxicity. However, nausea, vomiting, diarrhea, pyrexia, stomatitis, and esophagitis/dysphagia are excluded (Grade 3 nausea, vomiting, diarrhea, and pyrexia that cannot be controlled with antiemetic, antidiarrheal, or antifebrile agents are regarded as DLTs)
Grade 3 or higher stomatitis, esophagitis, and dysphagia that persist for >= 4 days
measure: Hematologic Remission Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 4 Weeks)
time frame: Up to 60 weeks
description: Definition
Complete remission (CR) Bone marrow: <= 5% myeloblasts; normal maturation of all cell lines Peripheral blood: Hemoglobin (Hgb) >= 11 g/dL, Platelets >= 100×10^9/L, Neutrophils >= 1.0×10^9/L, Blasts 0%
Partial remission (PR) Same as CR criteria except bone marrow blasts decreased by >= 50% over pretreatment but still > 5%
Marrow CR Bone marrow: <= 5% myeloblasts and decrease by >= 50% over pretreatment Peripheral blood: will be noted in addition to marrow CR
Stable disease Failure to achieve at least PR, but no evidence of progression for > 8 wks
Disease progression
Patients with:
Less than 5% blasts: >= 50% increase in blasts to > 5% blasts 5%-10% blasts: >= 50% increase to > 10% blasts 10%-20% blasts: >= 50% increase to > 20% blasts 20%-30% blasts: >= 50% increase to > 30% blasts
Any of the following:
At least 50% decrement from maximum remission/response in granulocytes or platelets Reduction in Hgb by >= 2 g/dL Transfusion dependence
measure: Hematologic Improvement Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 8 Weeks)
time frame: Up to 60 weeks
description: Definition
Hematologic Improvement Erythrocyte (HI-E):
Hgb increase by >= 1.5 g/dL Relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. Only RBC transfusions given for a Hgb of <= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation
Hematologic Improvement Platelet (HI-P):
Absolute increase of >= 30×10^9/L for patients starting with > 20×10^9/L platelets Increase from < 20×10^9/L to > 20×10^9/L and by at least 100%
Hematologic Improvement Neutrophil (HI-N):
At least 100% increase and an absolute increase > 0.5×10^9/L
Progressive disease / Relapse:
At least 1 of the following:
At least 50% decrement from maximum response levels in granulocytes or platelets Reduction in Hgb by >= 1.5 g/dL Transfusion dependence
measure: Maximum Tolerated Dose (MTD)
time frame: Up to 16 weeks
description: MTD was investigated with an index of DLT
arm group label: SyB L-1101
arm group type: Experimental
description: In Cohort 1, SyB L-1101 1200 mg/day group, Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.
In Cohort 2, SyB L-1101 1800 mg/day group, Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.
For both Cohorts, the treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.
intervention type: Drug
intervention name: SyB L-1101
description: SyB L-1101（rigosertib sodium） will be administered to two cohorts at either 1200 mg/day or 1800 mg/day.
The dose will be administered intravenously for 72 continuous hours (3 days), followed by 11-day observation period. The treatment period of 14 days (3 days of administration + 11 days of observation) constitutes 1 cycle.
The study will involve treatment through the second cycle, but treatment can be continued for 3 or more cycles if conditions for continued administration are satisfied.
arm group label: SyB L-1101
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 