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

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ClinicalTrials.gov Identifier: NCT02914938
Recruitment Status : Recruiting
First Posted : September 26, 2016
Last Update Posted : May 3, 2019
Sponsor:
Information provided by (Responsible Party):
MEI Pharma, Inc.

Study Description
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Brief 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

Condition or disease Intervention/treatment Phase
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) Drug: ME-401 Drug: Rituximab Drug: Zanubrutinib Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 177 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model 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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2016
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arms and Interventions
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Arm Intervention/treatment
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 Name: 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 (includes 3 cohorts up to 74 subjects).
 Drug: ME-401
60 mg

Drug: Zanubrutinib
160 mg bid


Outcome Measures
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Primary Outcome Measures :
  1. 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%.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Determine the DLTs of ME-401 plus zanubrutinib [ Time Frame: within the first 28 days ]
    DLTs will be measured by the number of treatment related AEs that occur within the first 28 days of ME-401 plus zanubrutinib

  7. 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


Secondary Outcome Measures :
  1. 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

  2. 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).

  3. Evaluate the (AUC) PK of ME-401 alone [ Time Frame: 2 years ]
    Determined by the Area Under the Concentration time curve (AUC)

  4. Evaluate the PK (Cmax) of ME-401 alone [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)

  5. 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)

  6. Evaluate the PK (AUC) of ME-401 with rituximab [ Time Frame: 2 years ]
    Determined by the Area Under the Concentration time curve (AUC)

  7. Evaluate the PK (Cmax) of ME-401 with rituximab [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)

  8. 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)

  9. 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)

  10. Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02914938


Contacts
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Contact: Lisa McColley 402-238-2615 lmccolley@clinipace.com
Contact: MEI Pharma 858-369-7100 patients@meipharma.com

Locations
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United States, California
Compassionate Care Recruiting
Corona, California, United States, 92708
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Stony Brook Recruiting
Stony Brook, New York, United States, 11794
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Vanderbilt Recruiting
Nashville, Tennessee, United States, 37240
United States, Washington
Swedish Cancer Center Recruiting
Seattle, Washington, United States, 98104
United States, Wisconsin
Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Switzerland
lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH Recruiting
Bellinzona, Switzerland
Sponsors and Collaborators
MEI Pharma, Inc.
More Information
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Responsible Party: MEI Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02914938     History of Changes
Other Study ID Numbers: ME-401-002
First Posted: September 26, 2016    Key Record Dates
Last Update Posted: May 3, 2019
Last Verified: June 2018

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Leukemia
Leukemia, B-Cell
Rituximab
Zanubrutinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action