A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma
- Conditions
- Chronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)Marginal Zone B Cell LymphomaHigh Grade Non-Hodgkin's LymphomaMantle Cell Lymphoma (MCL)Follicular Lymphoma (FL)Diffuse Large B-cell Lymphoma (DLBCL)
- Interventions
- Registration Number
- NCT02914938
- Lead Sponsor
- MEI Pharma, Inc.
- Brief Summary
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
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 97
Not provided
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ME-401 Alone ME-401 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. ME-401 in Combination with Rituximab ME-401 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. ME-401 in Combination with Zanubrutinib ME-401 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). ME-401 in Combination with Rituximab 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. ME-401 in Combination with Zanubrutinib 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).
- Primary Outcome Measures
Name Time Method Minimum Biologically Effective Dose (mBED) of ME-401 alone 1 year The mBED will be defined as the dose that is safe and that achieves an objective response rate that is not less than 30%.
Maximally Tolerated Dose (MTD) of ME-401 alone 1 year The MTD will be determined as the maximum dose that is safe. DLT rate closest to .25 and not to exceed 2 DLTs in 6 subjects
Determine the MTD of ME-401 plus zanubrutinib 1 year The MTD of ME-401 is defined as the dose level with a DLT rate closest to 0.25.
Determine the DLTs of ME-401 plus zanubrutinib within the first 56 days DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 plus zanubrutinib
Evaluate the safety and tolerability of ME-401 plus zanubrutinib 1 year Safety and tolerability will be measured by the number of treatment related AEs
Dose Limiting Toxicities (DLTs) of ME-401 alone within the first 56 days DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 administration, is considered clinically significant by the P.I. and occurs in the presence of supportive care
Evaluate the safety and tolerability of ME-401 plus rituximab 1 year Safety and tolerability will be measured by the number of treatment related AEs
- Secondary Outcome Measures
Name Time Method Evaluate the PK (Cmax) of ME-401 alone 2 years Determined by Peak Plasma Concentration (Cmax)
Efficacy of ME-401 with rituximab 2 years The efficacy of ME-401 with Rituximab will be determined by the overall response (OR) of subjects calculated as the percent of subjects achieving a complete remission (CR), duration of response (DOR) or Progression Free survival (PFS) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL)
Evaluate the PK (AUC) of ME-401 with rituximab 2 years Determined by the Area Under the Concentration time curve (AUC)
Evaluate the PK (Cmax) of ME-401 with rituximab 2 years Determined by Peak Plasma Concentration (Cmax)
Efficacy of ME-401 with zanubrutinib 2 years The efficacy of ME-401 with zanubrutinib will be assessed by the overall response (OR) of subjects calculated as the percent of subjects achieving a complete remission (CR), Duration of response (DOR) and progression free survival (PFS)
Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib 2 years Determined by the Area Under the Concentration time curve (AUC)
Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib 2 years Determined by Peak Plasma Concentration (Cmax)
Safety profile of ME-401 alone 1 year Safety profile will be measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Efficacy of ME-401 alone as assessed by (OR) 2 years The efficacy of ME-401 alone will be assessed by the overall response (OR) of subjects which is calculated as the percent of subjects achieving complete response (CR), minimal disease negativity (MRD), duration of response (DOR) and progression free survival (PFS).
Evaluate the (AUC) PK of ME-401 alone 2 years Determined by the Area Under the Concentration time curve (AUC)
Trial Locations
- Locations (18)
Swedish Cancer Institute
🇺🇸Issaquah, Washington, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Compassionate Care
🇺🇸Corona, California, United States
Memorial Sloan Kettering
🇺🇸Uniondale, New York, United States
Vanderbilt
🇺🇸Nashville, Tennessee, United States
Dana Farber
🇺🇸Boston, Massachusetts, United States
Stony Brook
🇺🇸Stony Brook, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Sylvester Comprehensive Cancer Center (Univ of Miami School of Med)
🇺🇸Miami, Florida, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Swedish Cancer Center
🇺🇸Seattle, Washington, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH
🇨ðŸ‡Bellinzona, Switzerland
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
NYU Langone Laura & Isaac - Perlmutter Cancer Center
🇺🇸New York, New York, United States
University of Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States