Clinical Trials /

Study of IV CBL0137 in Previously Treated Hematological Subjects

NCT02931110

Description:

This clinical trial is a Phase 1, open-label, sequential-group, dose-escalation (Part 1) and cohort-expansion study (Part 2) evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of intravenously (IV) administered CBL0137 in participants with previously treated hematological malignancies.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Mantle Cell Lymphoma
  • Multiple Myeloma
  • Small Lymphocytic Leukemia
Recruiting Status:

Suspended

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of IV CBL0137 in Previously Treated Hematological Subjects
  • Official Title: A Phase 1 Dose-Escalation and Cohort-Expansion Study of Intravenous CBL0137 in Subjects With Previously Treated Hematological Cancers

Clinical Trial IDs

  • ORG STUDY ID: I137-102
  • NCT ID: NCT02931110

Conditions

  • Hematological Malignancies

Interventions

DrugSynonymsArms
CBL0137CBL0137 Dose Escalation

Purpose

This clinical trial is a Phase 1, open-label, sequential-group, dose-escalation (Part 1) and cohort-expansion study (Part 2) evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CBL0137. The study will evaluate CBL0137 administered IV weekly on Days 1 and 8 of repeated 21 day treatment cycles in subjects with previously treated hematological malignancies.

Detailed Description

      Part 1 of the study will evaluate the safety and pharmacology of a range of CBL0137 doses
      administered IV in subjects with previously treated lymphomas, including diffuse large B-cell
      lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), or Hodgkin lymphoma
      (HL).

      Part 2 of the study provides cohort expansion to further explore the safety, pharmacology,
      and clinical activity of CBL0137 monotherapy in subjects with specific previously treated
      hematological cancers, including DLBCL, FL, MCL, HL, chronic lymphocytic leukemia/small
      lymphocytic lymphoma (CLL/SLL), acute lymphoblastic leukemia (ALL), acute myeloid leukemia
      (AML), and multiple myeloma (MM).
    

Trial Arms

NameTypeDescriptionInterventions
CBL0137 Dose EscalationExperimentalDose Level 1: 150mg/m2, IV Dose Level 2: 180mg/m2, IV Dose Level 3: 240mg/m2, IV Dose Level 4: 320mg/m2, IV Dose Level 5: 400mg/m2, IV Dose Level 6: 540mg/m2, IV Dose Level 7: 650mg/m2, IV Dose Level 8: 780mg/m2, IV Dose Level 9: 950mg/m2, IV Dose Level 10: 1150mg/m2, IV Dose Level 11: 1400mg/m2, IV Dose Level 12: 1700mg/m2, IV Dose Level 13: 2000mg/m2, IV Dose Level 14: 2400mg/m2, IV Dose Level 15: 2900mg/m2, IV Dose Level 16: 3500mg/m2, IV
  • CBL0137

Eligibility Criteria

        Inclusion Criteria:

          -  Presence of an active hematological malignancy:

               -  Part 1 (Dose Escalation): Diagnosis of B-cell DLBCL, FL, MCL, HL, CLL/SLL or MM
                  as documented by medical records.

               -  Part 2 (Cohort Expansion): Diagnosis of DLBCL, FL, MCL, HL, CLL/SLL, ALL, MM, or
                  AML as documented in medical records.

          -  Requirement for therapy of the hematological malignancy due to disease-related
             symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive
             disease.

          -  Hematological malignancy has been previously treated, has relapsed after or progressed
             during prior therapy, and has limited potential for benefit from currently available
             therapy, including hematopoietic stem cell transplantation.

          -  Presence of measurable disease:

               -  For subjects with DLBCL, FL, MCL, HL, or CLL/SLL: presence of radiographically
                  measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the
                  presence of ≥1 lesion that measures ≥2.0 cm in the longest dimension [LD] and
                  ≥1.0 cm in the longest perpendicular dimension [LPD] as assessed by computed
                  tomography [CT]).

               -  For subjects with MM, measurable disease with serum monoclonal immunoglobulin
                  protein (M-protein) ≥1 g/dL, or urine M-protein protein ≥200 mg/24 hours, or
                  involved serum free light chain (SFLC) ≥10 mg/dL.

               -  For subjects with ALL or AML, presence of >5% blasts in the bone marrow (based on
                  a bone marrow aspirate/biopsy sample with ≥200 nucleated cells and the presence
                  of bone marrow spicules) and/or >1 x 109/L blasts in the peripheral blood (with
                  the restriction that peripheral blast count in subjects with AML must be <50 x
                  109/L prior to the start of study therapy).

        Exclusion Criteria:

          -  Rapidly progressive, clinically unstable central nervous system hematological
             malignancy. Note: Central nervous system evaluation is only required in subjects with
             known or suspected central nervous system malignancy.

          -  Significant cardiovascular disease, including myocardial infarction, arterial
             thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of
             study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical
             therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York
             Heart Association Class 3 or 4 congestive heart failure; uncontrolled Grade ≥3
             hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg)
             despite antihypertensive therapy; or history of congenital prolonged QT syndrome.

          -  Significant screening ECG abnormalities, including unstable cardiac arrhythmia
             requiring medication, atrial fibrillation/flutter, left bundle-branch block,
             2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ≥2
             bradycardia, or QT corrected for heart rate (QTc) >450 msec (for men) or >470 msec
             (for women).

          -  Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis or
             requirement for systemic anticoagulation with unfractionated heparin,
             low-molecular-weight heparin or heparin fractions (eg, enoxaparin, dalteparin,
             fondaparinux) or oral anticoagulants (eg, apixaban, rivaroxaban, dabigatran etexilate,
             warfarin). Note: Use of heparin or thrombolytic agents for local maintenance or
             clearance of a central venous catheter is permitted.

          -  Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper
             respiratory tract infections) at the time of start of study therapy. Note: Subjects
             with localized fungal infections of skin or nails are eligible.

        Please speak with Investigator for the complete Inclusion/Exclusion criteria.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximally tolerated dose and recommended Phase 2 does in patients with hematological malignancy
Time Frame:30 days after last dose
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incuron

Trial Keywords

  • Diffuse large B-cell lymphoma (DLBCL)
  • follicular lymphoma (FL)
  • mantle cell lymphoma (MCL)
  • Hodgkin lymphoma (HL)
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
  • Multiple myeloma (MM)

Last Updated

January 7, 2019