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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 : February 8, 2018
Sponsor:
Information provided by (Responsible Party):
MEI Pharma, Inc.

Brief Summary:
This is a two-arm, Phase 1b, open-label, dose escalation study of ME-401 alone and an open-label study of ME-401 in combination with rituximab in patients with relapsed/refractory B-cell malignancies.

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 Drug: ME-401 Drug: Rituximab Phase 1

Detailed Description:
This is a two-arm, Phase 1b, open-label, dose escalation study of ME-401 alone and an open-label study of ME-401 in combination with rituximab in patients with relapsed/refractory B-cell malignancies. The two arms of the study will be conducted in parallel, with subject allocation to ME-401 alone or ME-401 plus rituximab based on disease type and availability of an open enrollment slot in the dose escalation arm.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a two-arm, Phase 1b, open-label, dose escalation study of ME-401 alone and an open label study of ME-401 in combination with rituximab in patients with relapsed/refractory B-cell malignancies. The two arms of the study will be conducted in parallel, with subject allocation to ME-401 alone or ME-401 plus rituximab based on disease type and availability of an open enrollment slot in the dose escalation arm.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Two-Arm, Phase 1b, Open-Label, Dose Escalation Study of ME-401 in Subjects With Relapsed/Refractory CLL, SLL, or FL and an Open-Label Study of ME-401 With Rituximab in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL
Study Start Date : October 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Experimental: ME-401 Alone
This is an open label, dose escalation study with 4 planned dose levels of ME-401. There are 5 planned cohorts which each may enroll up to 12 subjects each.
Drug: ME-401
Experimental: ME-401 in Combination with Rituximab
This is an open-label study evaluating the safety, efficacy, and pharmacokinetics of ME-401 in combination with rituximab in patients with various B-cell malignancies. There are two planned cohorts which may enroll up to 72 subjects.
Drug: ME-401
Drug: Rituximab
IV infusion 375 mg/m2
Other Name: Rituxan




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


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 calculated as the percent of subjects achieving a complete remission (CR) or a complete remission with incomplete marrow recovery (CRi) or a partial response (PR) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL)

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

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

  5. Efficacy of ME-401 with Rituximab as assessed by (OR) [ Time Frame: 2 years ]
    The efficacy of ME-401 with Rituximab will be determined by the overall response of subjects calculated as the percent of subjects achieving a complete remission (CR) or a complete remission with incomplete marrow recovery (CRi) or a partial response (PR) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL)

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

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



Information from the National Library of Medicine

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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
  • Subject must have failed at least 1 prior 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:

    1. Relapsed disease: a subject who previously achieved a CR or PR, but demonstrated disease progression after a response duration of >6 months
    2. Refractory disease: a subject who demonstrated disease progression within 6 months of most recent therapy
  • No prior therapy with PI3Kδ inhibitors
  • No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was intolerant of BTK therapy
  • Subjects with CLL, SLL, FL, and MZL must have a failure of at least 1 prior 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

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

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
Contact: Lisa McColley 402-238-2615 lmccolley@clinipace.com
Contact: Ben McOmber 858-369-7125 bmcomber@meipharma.com

Locations
United States, California
Compassionate Care Recruiting
Corona, California, United States, 92708
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.

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: February 8, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-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
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents