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

• Status: Recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MEI Pharma, Inc.
• Collaborator: Clinipace LTD
• Treatments: Rituximab; Zanubrutinib

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)