A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma
Purpose
A Three-Arm Study of ME-401 in Subjects with Relapsed/Refractory CLL/SLL or FL, of ME-401 in Combination with Rituximab in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination with Zanubrutinib in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL
Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Small Lymphocytic Lymphoma (SLL)
- Follicular Lymphoma (FL)
- Marginal Zone B Cell Lymphoma
- Diffuse Large B-cell Lymphoma (DLBCL)
- High Grade Non-Hodgkin's Lymphoma
- Mantle Cell Lymphoma (MCL)
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
MEI-401 Alone: - Diagnosis of relapsed/refractory CLL and/or relapsed/refractory SLL or FL - No prior therapy with PI3Kd inhibitors - No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was intolerant of BTK therapy or subject had disease progression - Subjects with CLL/SLL must have prior treatment with BTK inhibitor and must have had progression or recurrence while on treatment of within 12 mos from BTK treatment - Subject must have failed at least 1 prior systemic therapy - QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (ms) - Left ventricular ejection fraction > 50% - For subjects, except those with CLL, must have at least one bi-dimensionally measurable nodal lesion >1.5 cm, as defined by Lugano Classification - Willingness to participate in collection of pharmacokinetic samples - A negative serum pregnancy test within 14 days of study Day 0, for females of childbearing potential Inclusion Criteria ME-401 in Combination with Rituximab - Diagnosis of relapsed/refractory CLL SLL or FL, MZL, DLBCL and high-grade B-cell lymphoma. Subjects must meet the following criteria for relapsed or refractory disease: - No prior therapy with PI3Kδ inhibitors - No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was intolerant of BTK therapy or subject had disease progression - Subjects with CLL, SLL, FL, and MZL must have a failure of at least 1 prior systemic therapy and be considered by the investigator a candidate for therapy with a rituximab-based regimen; subjects with DLBCL and high-grade B-cell lymphoma must have a failure of at least 2 prior therapies. - QT-interval corrected according to Fridericia's formula (QTcF) ≤450 milliseconds (ms) - Left ventricular ejection fraction > 50% - For subjects, except those with CLL, must have at least one bi-dimensionally measurable nodal lesion >1.5 cm, as defined by Lugano Classification - Willingness to participate in collection of pharmacokinetic samples - A negative serum pregnancy test within 14 days of study Day 0 for females of childbearing potential Inclusion Criteria ME-401 in Combination with Zanubrutinib - Diagnosis of relapsed/refractory CLL or histologically-confirmed relapsed/refractory SLL or FL, MZL, MCL, DLBCL NOS (germinal center B-cell type or activated B-cell type) - No prior therapy with PI3Kδ inhibitors - No prior therapy with BTK inhibitors - Subjects with CLL, SLL, FL, MCL, and MZL must have a failure of at least 1 prior systemic therapy, require treatment in the opinion of the investigator, and be considered by the investigator a candidate for therapy subjects with DLBCL and high-grade B-cell lymphoma must have a failure of at least 2 prior therapies - For subjects with SLL, FL, MZL, MCL, DLBCL: At least one bi dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by CT scan or MRI - QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (msec) - Left ventricular ejection fraction > 50% as measured by echocardiogram or multigated acquisition (MUGA) scan - Willingness to participate in collection of pharmacokinetic samples - For females of childbearing potential, a negative serum pregnancy test within 14 days of study Day 0
Exclusion Criteria
- Known histological transformation from CLL to an aggressive lymphoma - Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia - Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core antibody - Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody - Ongoing drug-induced pneumonitis - History of clinically significant cardiovascular abnormalities - History of severe bleeding disorders (ME-401 plus zanubrutinib arm only) - Known central nervous system (CNS) hemorrhage or stroke within 6 months prior to start of study drugs (ME-401 plus zanubrutinib arm only)
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- This is a three-arm study of ME-401 alone, of ME-401 in combination with rituximab, and of ME-401 in combination with zanubrutinib in subjects with relapsed/refractory CLL/SLL or B cell NHL. The 3 arms of the study will be conducted in parallel, with subject allocation to ME 401 alone, ME-401 plus rituximab, or ME 401 plus zanubrutinib based on disease type and availability of an open enrollment slot.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental ME-401 Alone |
This arm is an open-label, dose escalation study to determine the safety, efficacy and pharmacokinetics of ME-401 along with the mBED, MTD, and DLTs. There are 4 planned cohorts which may enroll up to 61 subjects. |
|
Experimental ME-401 in Combination with Rituximab |
The second arm is an open label study to evaluate the safety, efficacy, and pharmacokinetics of ME-401 in combination with rituximab in subjects with various B-cell malignancies. There are two planned cohorts which may enroll up to 30 subjects. |
|
Experimental ME-401 in Combination with Zanubrutinib |
The third arm is an open label study evaluating the safety, efficacy, MTD, DLT and pharmacokinetics of ME-401 in combination with zanubrutinib in subjects with various B-cell malignancies. This arm will include 2 stages: a safety evaluation stage (cohort of 6-12 subjects) and a disease-specific expansion cohort stage (up to 74 subjects). |
|
More Details
- Status
- Terminated
- Sponsor
- MEI Pharma, Inc.
Study Contact
Detailed Description
This is a three-arm study of ME-401 alone, of ME-401 in combination with rituximab, and of ME-401 in combination with zanubrutinib in subjects with relapsed/refractory CLL/SLL or B cell NHL. The 3 arms of the study will be conducted in parallel, with subject allocation to ME-401 alone, ME-401 plus rituximab, or ME-401 plus zanubrutinib based on disease type and availability of an open enrollment slot.