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

NCT ID: NCT02914938

Last Updated: 2023-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

97 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-31

Study Completion Date

2023-03-29

Brief Summary

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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

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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.

Conditions

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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)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ME-401 Alone

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.

Group Type EXPERIMENTAL

ME-401

Intervention Type DRUG

60 mg

ME-401 in Combination with 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.

Group Type EXPERIMENTAL

ME-401

Intervention Type DRUG

60 mg

Rituximab

Intervention Type DRUG

IV infusion 375 mg/m2

ME-401 in Combination with 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).

Group Type EXPERIMENTAL

ME-401

Intervention Type DRUG

60 mg

Zanubrutinib

Intervention Type DRUG

80 and 160 mg bid

Interventions

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ME-401

60 mg

Intervention Type DRUG

Rituximab

IV infusion 375 mg/m2

Intervention Type DRUG

Zanubrutinib

80 and 160 mg bid

Intervention Type DRUG

Other Intervention Names

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Rituxan

Eligibility Criteria

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Inclusion Criteria

* 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


* 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


* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MEI Pharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Arizona

Tucson, Arizona, United States

Site Status

Compassionate Care

Corona, California, United States

Site Status

Sylvester Comprehensive Cancer Center (Univ of Miami School of Med)

Miami, Florida, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana Farber

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering

Middletown, New Jersey, United States

Site Status

Memorial Sloan Kettering

Montvale, New Jersey, United States

Site Status

Memorial Sloan Kettering

Commack, New York, United States

Site Status

Memorial Sloan Kettering

Harrison, New York, United States

Site Status

NYU Langone Laura & Isaac - Perlmutter Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Stony Brook

Stony Brook, New York, United States

Site Status

Memorial Sloan Kettering

Uniondale, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Vanderbilt

Nashville, Tennessee, United States

Site Status

University of Southwestern Medical Center

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Swedish Cancer Institute

Edmonds, Washington, United States

Site Status

Swedish Cancer Institute

Issaquah, Washington, United States

Site Status

Swedish Cancer Center

Seattle, Washington, United States

Site Status

Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH

Bellinzona, , Switzerland

Site Status

Countries

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United States Switzerland

References

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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.

Reference Type DERIVED
PMID: 35835137 (View on PubMed)

Other Identifiers

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ME-401-002

Identifier Type: -

Identifier Source: org_study_id

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