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.
Part 1 of the study will evaluate the safety and pharmacology of a range of CBL0137 doses
administered IV in participants with previously treated lymphomas, including diffuse large
B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Hodgkin
lymphoma (HL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), or multiple
myeloma (MM). Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively
higher dose levels of CBL0137 using a standard 3+3 dose-escalation design. An additional 6
participants may be accrued at the maximum tolerated dose (MTD) or at the recommended dose
(RD) to confirm CBL0137 safety and pharmacology as a prelude to further clinical evaluation.
Part 2 of the study provides cohort expansion to further explore the safety, pharmacology,
and clinical activity of CBL0137 monotherapy in participants with specific previously treated
hematological cancers, including DLBCL, FL, MCL, HL, CLL/SLL, acute lymphoblastic leukemia
(ALL), acute myeloid leukemia (AML), and MM. Twelve evaluable participants with each disease
type may be enrolled.
- 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 and ≥1.0 cm
in the longest perpendicular dimension as assessed by computed tomography).
- 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 ≥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).
- Completion of all previous therapy (including surgery, radiotherapy, chemotherapy,
immunotherapy, or investigational therapy) for the treatment of cancer ≥2 weeks before
the start of study therapy. Note: For subjects with AML, the use of hydroxyurea for
management of leukocytosis is allowed in Cycle 1 if hydroxyurea is started prior to
the initiation of study therapy.
- Part 2 (Cohort Expansion): History of another malignancy except for the following:
adequately treated local basal cell or squamous cell carcinoma of the skin; adequately
treated carcinoma in situ without evidence of disease; adequately treated, papillary,
noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in
complete remission; or any other cancer that has been in complete remission for ≥2
- 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 gastrointestinal disease or bleeding
- 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.
- In subjects with prior progenitor cell transplantation, evidence of ongoing
Please speak with Investigator for the complete Inclusion/Exclusion criteria.