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

• Register: ClinicalTrials.gov
• Last refreshed on: 15 May 2023
• Main ID: NCT02914938
• Date of registration: 12/09/2016
• Prospective Registration: Yes
• Primary sponsor: MEI Pharma, Inc.
• Public title: A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma
• Scientific 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
• Date of first enrolment: October 2016
• Target sample size: 97
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02914938
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Switzerland, United States

Key inclusion & exclusion 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 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Diffuse Large B-cell Lymphoma (DLBCL)

Marginal Zone B Cell Lymphoma

Chronic Lymphocytic Leukemia (CLL)

High Grade Non-Hodgkin's Lymphoma

Mantle Cell Lymphoma (MCL)

Follicular Lymphoma (FL)

Small Lymphocytic Lymphoma (SLL)

Intervention(s)

Drug: ME-401

Drug: Zanubrutinib

Drug: Rituximab

Primary Outcome(s)

Dose Limiting Toxicities (DLTs) of ME-401 alone [Time Frame: within the first 56 days]

Evaluate the safety and tolerability of ME-401 plus rituximab [Time Frame: 1 year]

Maximally Tolerated Dose (MTD) of ME-401 alone [Time Frame: 1 year]

Evaluate the safety and tolerability of ME-401 plus zanubrutinib [Time Frame: 1 year]

Determine the MTD of ME-401 plus zanubrutinib [Time Frame: 1 year]

Determine the DLTs of ME-401 plus zanubrutinib [Time Frame: within the first 56 days]

Minimum Biologically Effective Dose (mBED) of ME-401 alone [Time Frame: 1 year]

Secondary Outcome(s)

Efficacy of ME-401 with zanubrutinib [Time Frame: 2 years]

Safety profile of ME-401 alone [Time Frame: 1 year]

Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib [Time Frame: 2 years]

Evaluate the PK (Cmax) of ME-401 alone [Time Frame: 2 years]

Efficacy of ME-401 with rituximab [Time Frame: 2 years]

Evaluate the (AUC) PK of ME-401 alone [Time Frame: 2 years]

Evaluate the PK (AUC) of ME-401 with rituximab [Time Frame: 2 years]

Evaluate the PK (Cmax) of ME-401 with rituximab [Time Frame: 2 years]

Efficacy of ME-401 alone as assessed by (OR) [Time Frame: 2 years]

Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib [Time Frame: 2 years]

Secondary ID(s)

ME-401-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors