<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/NCT02223598</url>
  </required_header>
  <id_info>
    <org_study_id>CLC-102</org_study_id>
    <nct_id>NCT02223598</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study Evaluating CB-5083 in Subjects With Lymphoid Hematological Malignancies</brief_title>
  <acronym>CLC-102</acronym>
  <official_title>A Phase 1, Dose-Escalation/Dose-Expansion Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamic Effects of Orally Administered CB-5083 in Subjects With Lymphoid Hematological Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cleave Biosciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cleave Biosciences, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety, tolerability, dose limiting toxicities,&#xD;
      and maximum tolerated dose of CB-5083 in subjects with lymphoid hematological malignancies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    MTD determined&#xD;
  </why_stopped>
  <start_date type="Actual">August 25, 2014</start_date>
  <completion_date type="Actual">July 26, 2017</completion_date>
  <primary_completion_date type="Actual">July 26, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine the dose limiting toxicities (DLTs) of oral CB-5083 in subjects with lymphoid hematological malignancies</measure>
    <time_frame>Dose Escalation Stage - the first 28 days of treatment (Cycle 1) with CB-5083</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the pharmacokinetic (PK) profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the AUC</measure>
    <time_frame>Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 in the second 28 days (Cycle 2) of treatment with CB-5083</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the Cmax</measure>
    <time_frame>Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the Cmin</measure>
    <time_frame>Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the Tmax</measure>
    <time_frame>Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the T1/2</measure>
    <time_frame>Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To confirm the safety and tolerability of oral CB-5083 administered to subjects with relapsed and refractory Multiple Myeloma at the maximum tolerated dose (MTD) at the end of the Dose Escalation Stage</measure>
    <time_frame>Dose Expansion Stage - from day 1 of Cycle 1 through 28 days after the patient's last cycle of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To confirm the safety and tolerability of oral CB-5083 administered to subjects with relapsed/refractory DLBCL or Waldenstrom Macroglobulinemia at the MTD</measure>
    <time_frame>Dose Expansion Stage - from day 1 of Cycle 1 through 28 days after the patient's last cycle of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the pharmacodynamic (PD) effects of CB-5083 in peripheral blood cells and cancer cells</measure>
    <time_frame>Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To further asses the PK profile of oral CB-5083 in subjects by measuring the AUC</measure>
    <time_frame>Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To further asses the PK profile of oral CB-5083 in subjects by measuring the Cmax</measure>
    <time_frame>Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To further asses the PK profile of oral CB-5083 in subjects by measuring the Cmin</measure>
    <time_frame>Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To further asses the PK profile of oral CB-5083 in subjects by measuring the Tmax</measure>
    <time_frame>Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To further asses the PK profile of oral CB-5083 in subjects by measuring the T1/2</measure>
    <time_frame>Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate preliminary efficacy of oral CB-5083 in subjects, using standard response criteria</measure>
    <time_frame>Dose Expansion Stages - at the end of each 28 day cycle of treatment</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>To assess the predictive value of potential baseline biomarkers for clinical trial subject enrichment strategies</measure>
    <time_frame>Dose Expansion Stages - within 28 days before day 1 of Cycle 1</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Lymphoid Hematological Malignancies</condition>
  <condition>Relapsed and Refractory Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Dose Escalation - CB-5083</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CB-5083 will be administered orally, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with lymphoid hematological malignancies</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion - CB-5083, Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CB-5083 will be administered orally, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with relapsed and refractory multiple myeloma; in addition, subjects who develop progressive disease at the end of Cycle 1, or beyond, may receive their current dose of CB-5083 in combination with oral or IV low dose Dexamethasone (40 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion - CB-5083</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CB-5083 will be administered orally, daily, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with diffuse large B-cell lymphoma (DLBCL) or Waldenstrom Macroglobulinemia, if such arm is opened, per Sponsor</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CB-5083</intervention_name>
    <arm_group_label>Dose Escalation - CB-5083</arm_group_label>
    <arm_group_label>Dose Expansion - CB-5083</arm_group_label>
    <arm_group_label>Dose Expansion - CB-5083, Dexamethasone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <arm_group_label>Dose Expansion - CB-5083, Dexamethasone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females ≥18 years of age at the time of signing the consent form.&#xD;
&#xD;
          2. Dose Escalation Phase: Have a documented diagnosis of a lymphoid hematological&#xD;
             malignancy as described by the 2008 World Health Organization (WHO) classification&#xD;
             that requires therapy and for which there is no standard of care or standard of care&#xD;
             is not expected to be effective. Subjects must not be candidates for anti-tumor&#xD;
             regimens known to provide clinical benefit.&#xD;
&#xD;
             MM Dose Expansion Cohort:&#xD;
&#xD;
          3. Must have a documented diagnosis of relapsed and refractory multiple myeloma defined&#xD;
             by the International Myeloma Working Group (IMWG) criteria.&#xD;
&#xD;
          4. Must have measurable disease defined as:&#xD;
&#xD;
               -  Serum M-protein ≥ 0.5g/dL of IgA or ≥ 1 g/dL of IgG, or&#xD;
&#xD;
               -  Urine M-protein ≥ 200 mg/24 hr, or&#xD;
&#xD;
               -  Involved FLC assay &gt; 10 mg/dL with abnormal FLC ratio.&#xD;
&#xD;
          5. Must have received at least 4 prior therapies, including an alkylating agent (unless&#xD;
             not clinically indicated), proteasome inhibitor, an immunomodulatory (IMiD) and CD38&#xD;
             targeted therapy. At least 3 prior therapies where CD38 targeted therapies are not&#xD;
             approved, not commercially accessible, contraindicated or refused by subject.&#xD;
&#xD;
             DLBCL Dose Expansion Arm:&#xD;
&#xD;
          6. Must have histologically confirmed DLBCL that is relapsed or refractory to previous&#xD;
             therapy.&#xD;
&#xD;
          7. Must have ≥1 measurable disease sites as defined by standard Lugano classification.&#xD;
&#xD;
          8. Must have received at least 2 prior therapies, including a CD20 targeted therapy,&#xD;
             alkylating agent or corticosteroid; subjects who are not eligible for high-dose&#xD;
             chemotherapy and autologous stem cell transplantation (HD-ASCT) are eligible with&#xD;
             exposure to at least 1 prior therapy.&#xD;
&#xD;
             Waldstrom's Macroglobulinemia Dose Expansion Arm:&#xD;
&#xD;
          9. Must have a confirmed diagnosis of WM as defined by the Second International Workshop,&#xD;
             with a clinical indication for treatment.&#xD;
&#xD;
         10. Must have measurable disease, defined as presence of serum immunoglobulin M (IgM) with&#xD;
             a minimum IgM level of ≥ 2 times the upper limit of each institution's normal value is&#xD;
             required.&#xD;
&#xD;
         11. Must have relapsed/refractory disease after receiving 1 or more lines of therapy,&#xD;
             including a Bruton tyrosine kinase (BTK) inhibitor (eg ibrutinib) if approved by the&#xD;
             local health authority and commercially accessible.&#xD;
&#xD;
             All Arms:&#xD;
&#xD;
         12. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.&#xD;
&#xD;
         13. Adequate bone marrow function without transfusion or growth factor support, defined&#xD;
             as:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1,000/μL;&#xD;
&#xD;
               -  Platelet count ≥ 50,000/μL;&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dL&#xD;
&#xD;
         14. Adequate organ function defined as:&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 mg/dL or creatinine clearance &gt; 45 mL/min according to&#xD;
                  Cockcroft-Gault formula; (If creatinine clearance calculated from a 24-hour urine&#xD;
                  sample is ≥45 mL/min, the subject will qualify for the study).&#xD;
&#xD;
               -  Serum total bilirubin ≤ 2.0 mg/dL (34.2 μmol/L); or &gt; 3.0 × upper limit of normal&#xD;
                  (ULN) for subjects with hereditary benign hyperbilirubinemia&#xD;
&#xD;
               -  AST (SGOT) ≤ 3 × the ULN;&#xD;
&#xD;
               -  ALT (SGPT) ≤ 3 × the ULN;&#xD;
&#xD;
         15. Subjects who are fertile agree to use an effective barrier method of birth control&#xD;
             (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female subjects&#xD;
             need a negative serum or urine pregnancy test within 7 days of study enrollment&#xD;
             (applies only if subject is of childbearing potential. Non-childbearing is defined as&#xD;
             ≥ 1 year postmenopausal or surgically sterilized).&#xD;
&#xD;
         16. Willing and able to provide written Informed Consent and adhere to study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with leukemia are excluded, with the exception of chronic lymphocytic&#xD;
             leukemia (CLL), who are allowed in the dose escalation phase. Subjects with Burkitt&#xD;
             lymphoma, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal gammopathy, and skin changes), or amyloidosis are also&#xD;
             excluded.&#xD;
&#xD;
          2. Clinically active central nervous system (CNS) cancer involvement. Imaging to exclude&#xD;
             CNS involvement not required.&#xD;
&#xD;
          3. Previous or concomitant malignancy, except for basal-cell or squamous cell carcinoma&#xD;
             of the skin or carcinoma-in-situ of the uterine cervix. Subjects with other&#xD;
             malignancies are eligible if they have remained disease free for at least 2 years&#xD;
             prior to study entry;&#xD;
&#xD;
          4. Use of any anti-cancer drug therapy within 14 days prior to Baseline (within 28 days&#xD;
             for monoclonal antibodies [eg anti-CD38]).&#xD;
&#xD;
          5. Use of any investigational agent within 28 days prior to Baseline.&#xD;
&#xD;
          6. Presence of clinically significant non-hematological toxicity of prior chemotherapy&#xD;
             that has not resolved to ≤ Grade 1 as determined by CTCAE v 4.0, with the exception of&#xD;
             alopecia and peripheral neuropathy. Note: Peripheral neuropathy &gt; Grade 2 plus pain,&#xD;
             or Grade 3 or Grade 4 are excluded.&#xD;
&#xD;
          7. Radiotherapy within 14 days prior to Baseline.&#xD;
&#xD;
          8. Major surgery within 6 weeks prior to Baseline. The subject must have recovered from&#xD;
             surgery and be without current complications of infection or dehiscence.&#xD;
&#xD;
          9. Peripheral autologous stem cell transplant within 12 weeks prior to Baseline; prior&#xD;
             allogeneic transplants within 16 weeks or chronic use of immunosuppressants.&#xD;
&#xD;
         10. Active infection requiring systemic therapy, including known human immunodeficiency&#xD;
             virus (HIV), acquired immunodeficiency syndrome-related illness, or active hepatitis B&#xD;
             virus (HBV) or hepatitis C virus (HCV) infection.&#xD;
&#xD;
         11. Major cardiac abnormalities as defined but not limited to the following: uncontrolled&#xD;
             angina or unstable life-threatening arrhythmias, history of myocardial infarction&#xD;
             within 12 weeks prior to Baseline, Class 3 or higher New York Heart Association (NYHA)&#xD;
             congestive heart failure, or severe cardiac insufficiency, persistent (3 consecutive&#xD;
             electrocardiograms (ECGs) performed ≥ 5 minutes apart) prolongation of the QTc&#xD;
             (Fridericia) interval to &gt; 480 msec.&#xD;
&#xD;
         12. Cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient&#xD;
             ischemic attack, or pulmonary embolism within 12 weeks prior to Baseline.&#xD;
&#xD;
         13. Major gastrointestinal (GI) disease as defined but not limited to the following:&#xD;
             history of inflammatory bowel disease or other illness resulting in chronic diarrhea,&#xD;
             known achlorhydria or history of GI surgery that could reduce the acidity of the&#xD;
             stomach, acute pancreatitis or cholecystitis within 6 months prior to Baseline, or GI&#xD;
             disease that may interfere with the absorption of orally-administered drugs.&#xD;
&#xD;
         14. Grade 3 or 4 eye disorder at study entry, unless stable and longstanding (&gt;3 months)&#xD;
             and unlikely to interfere with protocol-required ophthalmology assessments.&#xD;
&#xD;
         15. A condition that is expected to require concomitant use of any medication listed as&#xD;
             prohibited while on study.&#xD;
&#xD;
         16. Is a pregnant or lactating female.&#xD;
&#xD;
         17. Has any severe, acute, or chronic medical or psychiatric condition, or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or study&#xD;
             drug administration, may interfere with the informed consent process and/or with&#xD;
             compliance with the requirements of the study, or may interfere with the&#xD;
             interpretation of the study results and, in the Investigator's opinion, would make the&#xD;
             subject inappropriate for entry into this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RCCA MD</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars Cancer Centre, McGill University Health Centre</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>February 23, 2018</last_update_submitted>
  <last_update_submitted_qc>February 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lymphoid Hematological Malignancies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02223598
org study id: CLC-102
nct id: NCT02223598
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine the safety, tolerability, dose limiting toxicities,
      and maximum tolerated dose of CB-5083 in subjects with lymphoid hematological malignancies.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine the dose limiting toxicities (DLTs) of oral CB-5083 in subjects with lymphoid hematological malignancies
time frame: Dose Escalation Stage - the first 28 days of treatment (Cycle 1) with CB-5083
measure: To determine the pharmacokinetic (PK) profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the AUC
time frame: Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 in the second 28 days (Cycle 2) of treatment with CB-5083
measure: To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the Cmax
time frame: Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the Cmin
time frame: Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the Tmax
time frame: Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To determine the PK profile of oral CB-5083 in subjects with lymphoid hematological malignancies by measuring the T1/2
time frame: Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To confirm the safety and tolerability of oral CB-5083 administered to subjects with relapsed and refractory Multiple Myeloma at the maximum tolerated dose (MTD) at the end of the Dose Escalation Stage
time frame: Dose Expansion Stage - from day 1 of Cycle 1 through 28 days after the patient's last cycle of treatment
measure: To confirm the safety and tolerability of oral CB-5083 administered to subjects with relapsed/refractory DLBCL or Waldenstrom Macroglobulinemia at the MTD
time frame: Dose Expansion Stage - from day 1 of Cycle 1 through 28 days after the patient's last cycle of treatment
measure: To assess the pharmacodynamic (PD) effects of CB-5083 in peripheral blood cells and cancer cells
time frame: Dose Escalation and Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1
measure: To further asses the PK profile of oral CB-5083 in subjects by measuring the AUC
time frame: Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To further asses the PK profile of oral CB-5083 in subjects by measuring the Cmax
time frame: Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To further asses the PK profile of oral CB-5083 in subjects by measuring the Cmin
time frame: Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To further asses the PK profile of oral CB-5083 in subjects by measuring the Tmax
time frame: Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To further asses the PK profile of oral CB-5083 in subjects by measuring the T1/2
time frame: Dose Expansion Stages - days 1, 2, 4 and 5 of Cycle 1 and days 1 and 2 of Cycle 2 of treatment with CB-5083
measure: To evaluate preliminary efficacy of oral CB-5083 in subjects, using standard response criteria
time frame: Dose Expansion Stages - at the end of each 28 day cycle of treatment
measure: To assess the predictive value of potential baseline biomarkers for clinical trial subject enrichment strategies
time frame: Dose Expansion Stages - within 28 days before day 1 of Cycle 1
arm group label: Dose Escalation - CB-5083
arm group type: Experimental
description: CB-5083 will be administered orally, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with lymphoid hematological malignancies
arm group label: Dose Expansion - CB-5083, Dexamethasone
arm group type: Experimental
description: CB-5083 will be administered orally, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with relapsed and refractory multiple myeloma; in addition, subjects who develop progressive disease at the end of Cycle 1, or beyond, may receive their current dose of CB-5083 in combination with oral or IV low dose Dexamethasone (40 mg)
arm group label: Dose Expansion - CB-5083
arm group type: Experimental
description: CB-5083 will be administered orally, daily, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with diffuse large B-cell lymphoma (DLBCL) or Waldenstrom Macroglobulinemia, if such arm is opened, per Sponsor
intervention type: Drug
intervention name: CB-5083
arm group label: Dose Escalation - CB-5083
arm group label: Dose Expansion - CB-5083
arm group label: Dose Expansion - CB-5083, Dexamethasone
intervention type: Drug
intervention name: Dexamethasone
arm group label: Dose Expansion - CB-5083, Dexamethasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms
mesh term: Hematologic Neoplasms
mesh term: Dexamethasone