Study of IV CBL0137 in Previously Treated Hematological Subjects

Launched by INCURON · Oct 11, 2016

Keywords

ClinConnect Summary

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 dos...

Gender

ALL

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 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.
• Exclusion Criteria:
• • 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 years.
• • 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 gastrointestinal disease or bleeding diathesis.
• • 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 graft-versus-host disease.
• • Please speak with Investigator for the complete Inclusion/Exclusion criteria.