Clinical trial NCT02914938: A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma
Official title: A Three-Arm Study of ME-401 Monotherapy 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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)
Lead sponsor: MEI Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-26
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Minimum Biologically Effective Dose (mBED) of ME-401 alone
timeFrame: 1 year
measure: Maximally Tolerated Dose (MTD) of ME-401 alone
timeFrame: 1 year
measure: Dose Limiting Toxicities (DLTs) of ME-401 alone
timeFrame: within the first 56 days
measure: Evaluate the safety and tolerability of ME-401 plus rituximab
timeFrame: 1 year
measure: Determine the MTD of ME-401 plus zanubrutinib
timeFrame: 1 year
measure: Determine the DLTs of ME-401 plus zanubrutinib
timeFrame: within the first 56 days
measure: Evaluate the safety and tolerability of ME-401 plus zanubrutinib
timeFrame: 1 year
Secondary outcomes:
measure: Safety profile of ME-401 alone
timeFrame: 1 year
measure: Efficacy of ME-401 alone as assessed by (OR)
timeFrame: 2 years
measure: Evaluate the (AUC) PK of ME-401 alone
timeFrame: 2 years
measure: Evaluate the PK (Cmax) of ME-401 alone
timeFrame: 2 years
measure: Efficacy of ME-401 with rituximab
timeFrame: 2 years
measure: Evaluate the PK (AUC) of ME-401 with rituximab
timeFrame: 2 years
measure: Evaluate the PK (Cmax) of ME-401 with rituximab
timeFrame: 2 years
measure: Efficacy of ME-401 with zanubrutinib
timeFrame: 2 years
measure: Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib
timeFrame: 2 years
measure: Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib
timeFrame: 2 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Corona
country: United States
facility: Compassionate Care
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center (Univ of Miami School of Med)
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber
state: Massachusetts
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: NYU Langone Laura & Isaac - Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: University of Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Edmonds
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Center
state: Washington
city: Madison
country: United States
facility: Carbone Cancer Center
state: Wisconsin
city: Bellinzona
country: Switzerland
facility: lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH
Study officials:
References:
citation: Pagel JM, Soumerai JD, Reddy N, Jagadeesh D, Stathis A, Asch A, Salman H, Kenkre VP, Iasonos A, Llorin-Sangalang J, Li J, Zelenetz AD. Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial. Lancet Oncol. 2022 Aug;23(8):1021-1030. doi: 10.1016/S1470-2045(22)00333-3. Epub 2022 Jul 11.