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

May 5, 2023 updated by: MEI Pharma, Inc.

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
97

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bellinzona, Switzerland
        • lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona
    • California
      • Corona, California, United States, 92708
        • Compassionate Care
    • Florida
      • Miami, Florida, United States, 33136
        • Sylvester Comprehensive Cancer Center (Univ of Miami School of Med)
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU Langone Laura & Isaac - Perlmutter Cancer Center
      • Stony Brook, New York, United States, 11794
        • Stony brook
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37240
        • Vanderbilt
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Edmonds, Washington, United States, 98026
        • Swedish Cancer Institute
      • Issaquah, Washington, United States, 98029
        • Swedish Cancer Institute
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Carbone Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: ME-401
60 mg
Experimental: 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.
Drug: ME-401
60 mg
Drug: Rituximab
IV infusion 375 mg/m2
Other Names:
  • Rituxan
Experimental: 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).
Drug: ME-401
60 mg
Drug: Zanubrutinib
80 and 160 mg bid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Minimum Biologically Effective Dose (mBED) of ME-401 alone
Time Frame: 1 year
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
Maximally Tolerated Dose (MTD) of ME-401 alone
Time Frame: 1 year
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
Dose Limiting Toxicities (DLTs) of ME-401 alone
Time Frame: within the first 56 days
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
Evaluate the safety and tolerability of ME-401 plus rituximab
Time Frame: 1 year
Safety and tolerability will be measured by the number of treatment related AEs
1 year
Determine the MTD of ME-401 plus zanubrutinib
Time Frame: 1 year
The MTD of ME-401 is defined as the dose level with a DLT rate closest to 0.25.
1 year
Determine the DLTs of ME-401 plus zanubrutinib
Time Frame: within the first 56 days
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
Evaluate the safety and tolerability of ME-401 plus zanubrutinib
Time Frame: 1 year
Safety and tolerability will be measured by the number of treatment related AEs
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety profile of ME-401 alone
Time Frame: 1 year
Safety profile will be measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0
1 year
Efficacy of ME-401 alone as assessed by (OR)
Time Frame: 2 years
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
Evaluate the (AUC) PK of ME-401 alone
Time Frame: 2 years
Determined by the Area Under the Concentration time curve (AUC)
2 years
Evaluate the PK (Cmax) of ME-401 alone
Time Frame: 2 years
Determined by Peak Plasma Concentration (Cmax)
2 years
Efficacy of ME-401 with rituximab
Time Frame: 2 years
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
Evaluate the PK (AUC) of ME-401 with rituximab
Time Frame: 2 years
Determined by the Area Under the Concentration time curve (AUC)
2 years
Evaluate the PK (Cmax) of ME-401 with rituximab
Time Frame: 2 years
Determined by Peak Plasma Concentration (Cmax)
2 years
Efficacy of ME-401 with zanubrutinib
Time Frame: 2 years
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
Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib
Time Frame: 2 years
Determined by the Area Under the Concentration time curve (AUC)
2 years
Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib
Time Frame: 2 years
Determined by Peak Plasma Concentration (Cmax)
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MEI Pharma, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 29, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 29, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 12, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 9, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ME-401-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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