Clinical Trial - NCT02914938

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

Recruiting

Sponsor: MEI Pharma, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02914938

Protocol Info

Short Description: Phase 1 ME-401 in CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma
Long Description: A Phase 1b, Open-Label, Dose Escalation Study of ME-401 in Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Follicular Lymphoma (FL)
MGH Status: Open
Sponsor: MEI Pharma, Inc.
Disease Program: Lymphoma

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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 Title Intervention 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) ME-401 Rituximab Zanubrutinib Phase 1
Study Type Interventional
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

Primary Outcome Measures

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

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

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

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

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

Determine the DLTs of ME-401 plus zanubrutinib [Time Frame: within the first 28 days] [Designated as safety issue: ]

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


Secondary Outcome Measures

Safety profile of ME-401 alone [Time Frame: 1 year] [Designated as safety issue: ]

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

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

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

Efficacy of ME-401 with rituximab [Time Frame: 2 years] [Designated as safety issue: ]

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

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

Efficacy of ME-401 with zanubrutinib [Time Frame: 2 years] [Designated as safety issue: ]

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

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

Estimated Enrollment: 177
Study Start Date: October 2016
Estimated Study Completion Date: January 2022
Estimated Primary Completion Date: September 2021
Arms Assigned Interventions

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:Rituximab
IV infusion 375 mg/m2

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:Zanubrutinib
160 mg bid

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT02914938

Locations

  • United States, California
    • Compassionate Care Corona, California, United States, 92708
  • United States, Massachusetts
    • Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02114
  • United States, New York
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
    • Stony Brook Stony Brook, New York, United States, 11794
  • United States, Ohio
    • Cleveland Clinic Cleveland, Ohio, United States, 44195
  • United States, Oklahoma
    • Stephenson Cancer Center Oklahoma City, Oklahoma, United States, 73104
  • United States, Tennessee
    • Vanderbilt Nashville, Tennessee, United States, 37240
  • United States, Washington
    • Swedish Cancer Center Seattle, Washington, United States, 98104
  • United States, Wisconsin
    • Carbone Cancer Center Madison, Wisconsin, United States, 53792
  • Switzerland,
    • lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH Bellinzona, , Switzerland,

Sponsors and Collaborators

MEI Pharma, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02914938
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

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

Rituximab

Zanubrutinib

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019