A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02914938
• Other study ID #: ME-401-002
• Status: Terminated
• Phase: Phase 1
• Start date: October 2016
• Est. completion date: March 29, 2023

Study information

• Verified date: December 2022
• Source: MEI Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Terminated
• Enrollment: 97
• Est. completion date: March 29, 2023
• Est. primary completion date: March 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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, 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 PI3Kd 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)

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Diffuse Large B-cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• High Grade Non-Hodgkin's Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma (MCL)
• Marginal Zone B Cell Lymphoma
• Small Lymphocytic Lymphoma (SLL)

Intervention

Drug:
• ME-401
60 mg
• Rituximab
IV infusion 375 mg/m2
• Zanubrutinib
80 and 160 mg bid

Locations

Country	Name	City	State
Switzerland	lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH	Bellinzona
United States	Memorial Sloan Kettering	Basking Ridge	New Jersey
United States	Dana Farber	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Memorial Sloan Kettering	Commack	New York
United States	Compassionate Care	Corona	California
United States	University of Southwestern Medical Center	Dallas	Texas
United States	Swedish Cancer Institute	Edmonds	Washington
United States	Memorial Sloan Kettering	Harrison	New York
United States	MD Anderson Cancer Center	Houston	Texas
United States	Swedish Cancer Institute	Issaquah	Washington
United States	Carbone Cancer Center	Madison	Wisconsin
United States	Sylvester Comprehensive Cancer Center (Univ of Miami School of Med)	Miami	Florida
United States	Memorial Sloan Kettering	Middletown	New Jersey
United States	Memorial Sloan Kettering	Montvale	New Jersey
United States	Vanderbilt	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone Laura & Isaac - Perlmutter Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Swedish Cancer Center	Seattle	Washington
United States	Stony Brook	Stony Brook	New York
United States	University of Arizona	Tucson	Arizona
United States	Memorial Sloan Kettering	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
MEI Pharma, Inc.

Countries where clinical trial is conducted

United States,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Minimum Biologically Effective Dose (mBED) of ME-401 alone	The mBED will be defined as the dose that is safe and that achieves an objective response rate that is not less than 30%.	1 year
Primary	Maximally Tolerated Dose (MTD) of ME-401 alone	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	1 year
Primary	Dose Limiting Toxicities (DLTs) of ME-401 alone	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	within the first 56 days
Primary	Evaluate the safety and tolerability of ME-401 plus rituximab	Safety and tolerability will be measured by the number of treatment related AEs	1 year
Primary	Determine the MTD of ME-401 plus zanubrutinib	The MTD of ME-401 is defined as the dose level with a DLT rate closest to 0.25.	1 year
Primary	Determine the DLTs of ME-401 plus zanubrutinib	DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 plus zanubrutinib	within the first 56 days
Primary	Evaluate the safety and tolerability of ME-401 plus zanubrutinib	Safety and tolerability will be measured by the number of treatment related AEs	1 year
Secondary	Safety profile of ME-401 alone	Safety profile will be measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0	1 year
Secondary	Efficacy of ME-401 alone as assessed by (OR)	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).	2 years
Secondary	Evaluate the (AUC) PK of ME-401 alone	Determined by the Area Under the Concentration time curve (AUC)	2 years
Secondary	Evaluate the PK (Cmax) of ME-401 alone	Determined by Peak Plasma Concentration (Cmax)	2 years
Secondary	Efficacy of ME-401 with rituximab	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)	2 years
Secondary	Evaluate the PK (AUC) of ME-401 with rituximab	Determined by the Area Under the Concentration time curve (AUC)	2 years
Secondary	Evaluate the PK (Cmax) of ME-401 with rituximab	Determined by Peak Plasma Concentration (Cmax)	2 years
Secondary	Efficacy of ME-401 with zanubrutinib	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)	2 years
Secondary	Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib	Determined by the Area Under the Concentration time curve (AUC)	2 years
Secondary	Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib	Determined by Peak Plasma Concentration (Cmax)	2 years