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
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
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).
- 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
- 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
- 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).
- 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
- 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.