<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/NCT03018223</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-18766</org_study_id>
    <nct_id>NCT03018223</nct_id>
  </id_info>
  <brief_title>Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haplo PBSCT</brief_title>
  <official_title>A Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haploidentical Peripheral Blood Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out if a combination of drugs (these are called:&#xD;
      cyclophosphamide, sirolimus, and mycophenolate mofetil) will protect participants better&#xD;
      against graft vs. host disease (GVHD) after receiving a hematopoietic cell transplant from a&#xD;
      related partially matched (haploidentical) donor. As part of the treatment for their blood&#xD;
      cancer, participants need a hematopoietic cell transplantation (HCT) to improve their chances&#xD;
      of cure. In any HCT, after the stem cell infusion is given, a combination of drugs is needed&#xD;
      to prevent GVHD and facilitate acceptance of the graft.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Actual">March 18, 2021</completion_date>
  <primary_completion_date type="Actual">December 15, 2018</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Grade II-IV Acute Graft vs. Host Disease (GVHD)</measure>
    <time_frame>100 days post hematopoietic cell transplant (HCT)</time_frame>
    <description>Cumulative incidence of grade II-IV acute GVHD by day 100 after HCT. Acute GVHD organ staging and assessment of overall grade will use standard consensus criteria. The cumulative incidence of acute and chronic GVHD will be estimated, considering malignancy relapse and non-relapse death as competing risk events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Chronic GVHD</measure>
    <time_frame>1 year post HCT</time_frame>
    <description>Cumulative incidence of chronic GVHD by 1 year. Chronic GVHD diagnosis follow National Institutes of Health (NIH) Consensus guidelines.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 1 year post HCT</time_frame>
    <description>Overall survival is defined as time from transplant to death or last follow-up, and is reported as percentage of surviving participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to 1 year post HCT</time_frame>
    <description>Progression-free survival defined by the time interval from transplant to relapse/recurrence, to death or to last follow-up. Reported as percentage of participants who are disease free one year post HCT.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Non-Hodgkin's Lymphoma</condition>
  <condition>Acute Leukemia in Remission</condition>
  <condition>Chronic Myeloid Leukemia</condition>
  <condition>Primary Myelofibrosis</condition>
  <condition>Chronic Myelomonocytic Leukemia</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Hodgkin Lymphoma</condition>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.&#xD;
Conditioning regimen: To reduce heterogeneity, two commonly used myeloablative (MAC) and reduced intensity (RIC) regimens are permitted on this trial. Myeloablative conditioning: fludarabine, busulfan. Reduced intensity conditioning: fludarabine, cyclophosphamide, total body irradiation.&#xD;
Peripheral blood hematopoietic cell transplantation&#xD;
Graft vs. Host Disease (GVHD) prevention treatment: cyclophosphamide, mycophenolate mofetil, sirolimus.&#xD;
Growth factor support: G-CSF</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>Myeloablative conditioning: 40 mg/m^2 daily for 4 days. Dose will be adjusted for estimated creatinine clearance. Reduced intensity conditioning: 30 mg/m^2 daily on days -6, -5, -4, -3 and -2. Dose will be adjusted for estimated creatinine clearance.</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>Fludara, Oforta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan</intervention_name>
    <description>Myeloablative conditioning: IV dosing targeted for a daily total area under curve (AUC) 5300 mmol*min/L for 4 days. Busulfan AUC will be pharmacokinetically targeted. An AUC 3500 mmol*min/l may be considered in patients over 60 years of age or with multiple comorbidities. Chemotherapy may start on day -6 or day -5 depending on the day of admission (-6 for Wednesday admission, -5 for Sunday admission).</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>Busulfex, Myleran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Reduced intensity conditioning: 14.5 mg/kg/day on days -6, -5. GVHD prophylaxis: 50 mg/kg ideal body weight (IBW) daily dose will be given on days +3 and +4 post-transplant as an IV infusion over 1-2 hours.</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total body irradiation (TBI)</intervention_name>
    <description>Reduced intensity conditioning: 200 centigray (cGy) on day -1.</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>radiotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Hematopoietic Cell Transplantation (HCT)</intervention_name>
    <description>On day 0, patients will receive a peripheral blood hematopoietic cell graft.</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>cell graft</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus (SIR)</intervention_name>
    <description>GVHD prophylaxis: SIR will be administered as a 9 mg oral loading dose on day +5, followed by maintenance. SIR levels will be monitored and maintenance dosing adjusted as needed for a target trough level 8 to 14 ng/ml, per Moffitt BMT program standard practice. In the absence of acute GVHD, sirolimus taper will start on day +90 (+/- 10 days) and it is suggested to finish by day +180.</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>Rapamune</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate mofetil (MMF)</intervention_name>
    <description>GVHD prophylaxis: MMF will start on day +5 at a dose of 15 mg/kg every 8 hours IV with the maximum daily dose not to exceed 3 gm. MMF will be changed to orally (PO) and discontinued on day +35 (without taper) in the absence of acute GVHD.</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>CellCept</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Granulocyte-colony stimulating factor (G-CSF)</intervention_name>
    <description>Growth factor support: G-CSF will be given beginning on day 5 at a dose of 5 mcg/kg/day (rounding to the nearest vial dose), until absolute granulocyte count (ANC) is &gt; 1,000/mm^3 for three consecutive days. G-CSF may be given IV or subcutaneously.</description>
    <arm_group_label>Conditioning/HCT/GVHD Prophylaxis</arm_group_label>
    <other_name>Neupogen, Filgrastim</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patient Participants:&#xD;
&#xD;
          -  Age: Must be older than 18 years, no upper age limit.&#xD;
&#xD;
          -  Karnofsky performance status: Full intensity conditioning, 80-100%; reduced intensity&#xD;
             conditioning, 60-100%.&#xD;
&#xD;
          -  Vital organ function: a) Cardiac: Left ventricular ejection fraction must be &gt; 45%&#xD;
             assessed by multigated acquisition (MUGA) scan or echocardiogram. No myocardial&#xD;
             infarction within 6 months of transplant evaluation. b) Pulmonary: forced expiratory&#xD;
             volume at one second (FEV1), forced vital capacity (FVC), and adjusted diffusing&#xD;
             capacity of the lungs for carbon monoxide (DLCO) must be ≥ 50% of predicted values. c)&#xD;
             Liver: Transaminases (AST, ALT) less than 2 times upper limit of normal values. d)&#xD;
             Kidney: Estimated creatinine clearance ≥ 50 cc/min.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Included disease conditions and remission status: a) Acute leukemia in First Complete&#xD;
             Remission (CR1) or second/subsequent CR. b) Chronic myeloid leukemia, primary&#xD;
             myelofibrosis, chronic myelomonocytic leukemia. c) Int-2 or high risk myelodysplastic&#xD;
             syndrome (MDS). d) Hodgkin lymphoma beyond CR1 with chemosensitive disease, Stable&#xD;
             Disease (SD) may be included if no mass &gt;3 cm. e) Non-Hodgkin lymphoma in high risk&#xD;
             CR1 or subsequent CR (by clinical, cytogenetic or molecular criteria), primary&#xD;
             induction failure (PIF) or relapsed with chemosensitive disease. SD may be included if&#xD;
             no mass &gt;3 cm. f) Multiple myeloma in CR/Very Good Partial Response (VGPR).&#xD;
&#xD;
        Donor Participants:&#xD;
&#xD;
          -  Per Moffitt Cancer Center (MCC) Blood and Marrow Transplant (BMT) program practices,&#xD;
             an allele level matched (8/8 HLA A, B, C and DR) sibling or unrelated donor is&#xD;
             preferred. If a matched donor is not found, mismatched unrelated or haploidentical&#xD;
             donors may be considered.&#xD;
&#xD;
          -  If a haploidentical donor is considered, parents, children, full siblings and in&#xD;
             selected cases, extended family, will have high resolution typing at the MCC HLA&#xD;
             laboratory. A familiar haploidentical donor is chosen among those who share at least&#xD;
             one HLA-A, B, C, DRB1 and DQB1 haplotype with the patient.&#xD;
&#xD;
          -  Patient will be screened for antibodies targeting mismatched HLA antigens in potential&#xD;
             haploidentical donors (donor specific antibodies, DSA). Antibody screen and&#xD;
             confirmatory testing using Luminex single antigen-bead test will be done.&#xD;
&#xD;
          -  Among several potential donors, will choose in order of priority: a) Matched&#xD;
             cytomegalovirus (CMV) immunoglobulin G (IgG) serologic status between donor and&#xD;
             recipient. b) ABO blood group system-matched donor preferred, then minor ABO mismatch,&#xD;
             then major ABO mismatch. c) Younger donor preferred: child, then sibling, and then&#xD;
             parent. d) For male recipient, male donor will be preferred. Avoid mother as a donor&#xD;
             unless no other choices.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patient Participants:&#xD;
&#xD;
          -  Uncontrolled active bacterial, viral, fungal infection.&#xD;
&#xD;
          -  Prior allogeneic HCT.&#xD;
&#xD;
          -  Unwilling to comply with study requirements.&#xD;
&#xD;
          -  Active, progressive or advanced disease based on diagnosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nelli Bejanyan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://moffitt.org/clinical-trials-research/</url>
    <description>Moffitt Cancer Center Clinical Trials website</description>
  </link>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <results_first_submitted>December 6, 2019</results_first_submitted>
  <results_first_submitted_qc>January 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 21, 2020</results_first_posted>
  <last_update_submitted>September 14, 2021</last_update_submitted>
  <last_update_submitted_qc>September 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute leukemia in CR</keyword>
  <keyword>Chronic myeloid leukemia</keyword>
  <keyword>Non-Hodgkin lymphoma in high risk</keyword>
  <keyword>Graft vs. Host Disease</keyword>
  <keyword>GVHD</keyword>
  <keyword>Hematopoietic cell transplant (HCT)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Chronic</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Juvenile</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Primary Myelofibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Lenograstim</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03018223/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Conditioning/HCT/GVHD Prophylaxis</title>
          <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants</population>
      <group_list>
        <group group_id="B1">
          <title>Conditioning/HCT/GVHD Prophylaxis</title>
          <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.5" lower_limit="23" upper_limit="74"/>
                  </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="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Grade II-IV Acute Graft vs. Host Disease (GVHD)</title>
        <description>Cumulative incidence of grade II-IV acute GVHD by day 100 after HCT. Acute GVHD organ staging and assessment of overall grade will use standard consensus criteria. The cumulative incidence of acute and chronic GVHD will be estimated, considering malignancy relapse and non-relapse death as competing risk events.</description>
        <time_frame>100 days post hematopoietic cell transplant (HCT)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conditioning/HCT/GVHD Prophylaxis</title>
            <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Grade II-IV Acute Graft vs. Host Disease (GVHD)</title>
          <description>Cumulative incidence of grade II-IV acute GVHD by day 100 after HCT. Acute GVHD organ staging and assessment of overall grade will use standard consensus criteria. The cumulative incidence of acute and chronic GVHD will be estimated, considering malignancy relapse and non-relapse death as competing risk events.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.8" lower_limit="7.5" upper_limit="34.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Chronic GVHD</title>
        <description>Cumulative incidence of chronic GVHD by 1 year. Chronic GVHD diagnosis follow National Institutes of Health (NIH) Consensus guidelines.</description>
        <time_frame>1 year post HCT</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conditioning/HCT/GVHD Prophylaxis</title>
            <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Chronic GVHD</title>
          <description>Cumulative incidence of chronic GVHD by 1 year. Chronic GVHD diagnosis follow National Institutes of Health (NIH) Consensus guidelines.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" lower_limit="7.9" upper_limit="36.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall survival is defined as time from transplant to death or last follow-up, and is reported as percentage of surviving participants.</description>
        <time_frame>Up to 1 year post HCT</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conditioning/HCT/GVHD Prophylaxis</title>
            <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall survival is defined as time from transplant to death or last follow-up, and is reported as percentage of surviving participants.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.2" lower_limit="55.5" upper_limit="88.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>Progression-free survival defined by the time interval from transplant to relapse/recurrence, to death or to last follow-up. Reported as percentage of participants who are disease free one year post HCT.</description>
        <time_frame>Up to 1 year post HCT</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Conditioning/HCT/GVHD Prophylaxis</title>
            <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>Progression-free survival defined by the time interval from transplant to relapse/recurrence, to death or to last follow-up. Reported as percentage of participants who are disease free one year post HCT.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.6" lower_limit="41.3" upper_limit="77.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years, 7 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Conditioning/HCT/GVHD Prophylaxis</title>
          <description>Pre-HCT Conditioning, HCT, GVHD Prophylaxis.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders -Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colonic perforation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Immune system disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Infections and infestations -Other</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Portal vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and Infestations - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Nelli Bejanyan, MD</name_or_title>
      <organization>Moffitt Cancer Center</organization>
      <phone>813-745-7208</phone>
      <email>Nellie.Bejanyan@moffitt.org</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/NCT03018223
org study id: MCC-18766
nct id: NCT03018223
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to find out if a combination of drugs (these are called:
      cyclophosphamide, sirolimus, and mycophenolate mofetil) will protect participants better
      against graft vs. host disease (GVHD) after receiving a hematopoietic cell transplant from a
      related partially matched (haploidentical) donor. As part of the treatment for their blood
      cancer, participants need a hematopoietic cell transplantation (HCT) to improve their chances
      of cure. In any HCT, after the stem cell infusion is given, a combination of drugs is needed
      to prevent GVHD and facilitate acceptance of the graft.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Incidence of Grade II-IV Acute Graft vs. Host Disease (GVHD)
time frame: 100 days post hematopoietic cell transplant (HCT)
description: Cumulative incidence of grade II-IV acute GVHD by day 100 after HCT. Acute GVHD organ staging and assessment of overall grade will use standard consensus criteria. The cumulative incidence of acute and chronic GVHD will be estimated, considering malignancy relapse and non-relapse death as competing risk events.
measure: Incidence of Chronic GVHD
time frame: 1 year post HCT
description: Cumulative incidence of chronic GVHD by 1 year. Chronic GVHD diagnosis follow National Institutes of Health (NIH) Consensus guidelines.
measure: Overall Survival (OS)
time frame: Up to 1 year post HCT
description: Overall survival is defined as time from transplant to death or last follow-up, and is reported as percentage of surviving participants.
measure: Progression Free Survival (PFS)
time frame: Up to 1 year post HCT
description: Progression-free survival defined by the time interval from transplant to relapse/recurrence, to death or to last follow-up. Reported as percentage of participants who are disease free one year post HCT.
arm group label: Conditioning/HCT/GVHD Prophylaxis
arm group type: Experimental
description: Pre-HCT Conditioning, HCT, GVHD Prophylaxis.
Conditioning regimen: To reduce heterogeneity, two commonly used myeloablative (MAC) and reduced intensity (RIC) regimens are permitted on this trial. Myeloablative conditioning: fludarabine, busulfan. Reduced intensity conditioning: fludarabine, cyclophosphamide, total body irradiation.
Peripheral blood hematopoietic cell transplantation
Graft vs. Host Disease (GVHD) prevention treatment: cyclophosphamide, mycophenolate mofetil, sirolimus.
Growth factor support: G-CSF
intervention type: Drug
intervention name: Fludarabine
description: Myeloablative conditioning: 40 mg/m^2 daily for 4 days. Dose will be adjusted for estimated creatinine clearance. Reduced intensity conditioning: 30 mg/m^2 daily on days -6, -5, -4, -3 and -2. Dose will be adjusted for estimated creatinine clearance.
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: Fludara, Oforta
intervention type: Drug
intervention name: Busulfan
description: Myeloablative conditioning: IV dosing targeted for a daily total area under curve (AUC) 5300 mmol*min/L for 4 days. Busulfan AUC will be pharmacokinetically targeted. An AUC 3500 mmol*min/l may be considered in patients over 60 years of age or with multiple comorbidities. Chemotherapy may start on day -6 or day -5 depending on the day of admission (-6 for Wednesday admission, -5 for Sunday admission).
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: Busulfex, Myleran
intervention type: Drug
intervention name: Cyclophosphamide
description: Reduced intensity conditioning: 14.5 mg/kg/day on days -6, -5. GVHD prophylaxis: 50 mg/kg ideal body weight (IBW) daily dose will be given on days +3 and +4 post-transplant as an IV infusion over 1-2 hours.
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: Cytoxan
intervention type: Radiation
intervention name: Total body irradiation (TBI)
description: Reduced intensity conditioning: 200 centigray (cGy) on day -1.
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: radiotherapy
intervention type: Procedure
intervention name: Peripheral Blood Hematopoietic Cell Transplantation (HCT)
description: On day 0, patients will receive a peripheral blood hematopoietic cell graft.
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: cell graft
intervention type: Drug
intervention name: Sirolimus (SIR)
description: GVHD prophylaxis: SIR will be administered as a 9 mg oral loading dose on day +5, followed by maintenance. SIR levels will be monitored and maintenance dosing adjusted as needed for a target trough level 8 to 14 ng/ml, per Moffitt BMT program standard practice. In the absence of acute GVHD, sirolimus taper will start on day +90 (+/- 10 days) and it is suggested to finish by day +180.
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: Rapamune
intervention type: Drug
intervention name: Mycophenolate mofetil (MMF)
description: GVHD prophylaxis: MMF will start on day +5 at a dose of 15 mg/kg every 8 hours IV with the maximum daily dose not to exceed 3 gm. MMF will be changed to orally (PO) and discontinued on day +35 (without taper) in the absence of acute GVHD.
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: CellCept
intervention type: Drug
intervention name: Granulocyte-colony stimulating factor (G-CSF)
description: Growth factor support: G-CSF will be given beginning on day 5 at a dose of 5 mcg/kg/day (rounding to the nearest vial dose), until absolute granulocyte count (ANC) is > 1,000/mm^3 for three consecutive days. G-CSF may be given IV or subcutaneously.
arm group label: Conditioning/HCT/GVHD Prophylaxis
other name: Neupogen, Filgrastim
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Nelli Bejanyan, M.D.
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
country: United States
url: https://moffitt.org/clinical-trials-research/
description: Moffitt Cancer Center Clinical Trials website
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Multiple Myeloma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Leukemia, Myelomonocytic, Chronic
mesh term: Leukemia, Myelomonocytic, Juvenile
mesh term: Myelodysplastic Syndromes
mesh term: Primary Myelofibrosis
mesh term: Mycophenolic Acid
mesh term: Sirolimus
mesh term: Cyclophosphamide
mesh term: Busulfan
mesh term: Fludarabine
mesh term: Lenograstim
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 