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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.

Tracking Information
First Submitted Date  ICMJE September 12, 2016
First Posted Date  ICMJE September 26, 2016
Last Update Posted Date May 3, 2019
Study Start Date  ICMJE October 2016
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • 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%.
  • 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
  • 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
  • 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
  • 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.
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2016)
  • Minimum Biologically Effective Dose (mBED) of ME-401 [ Time Frame: 1 year ]
    The mBED will be defined as the dose that is safe and that achieves an objective response rate
  • Maximally Tolerated Dose (MTD) of ME-401 [ Time Frame: 1 year ]
    The MTD will be determined as the dose level with a DLT rate closest to .25
  • Dose Limiting Toxicities (DLTs) of ME-401 [ Time Frame: within the first 56 days ]
    DLTs will be measured by the number of 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
Change History Complete list of historical versions of study NCT02914938 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • 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
  • 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).
  • Evaluate the (AUC) PK of ME-401 alone [ Time Frame: 2 years ]
    Determined by the Area Under the Concentration time curve (AUC)
  • Evaluate the PK (Cmax) of ME-401 alone [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)
  • 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)
  • Evaluate the PK (AUC) of ME-401 with rituximab [ Time Frame: 2 years ]
    Determined by the Area Under the Concentration time curve (AUC)
  • Evaluate the PK (Cmax) of ME-401 with rituximab [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)
  • 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)
  • 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)
  • Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2016)
  • Safety profile of ME-401 [ Time Frame: 1 year ]
    Safety profile will be measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0
  • The Recommended Phase 2 Dose (RP2D) [ Time Frame: 2 year ]
    The RP2D will be determined by the evaluation of safety and efficacy data
  • Peak Plasma Concentration (Cmax) [ Time Frame: 2 years ]
  • AUC (area under the concentration time curve) [ Time Frame: 2 years ]
  • Efficacy of ME-401 [ Time Frame: 2 years ]
    The efficacy of ME-401 assessed by the overall response (OR)
  • Efficacy of ME-401 [ Time Frame: 2 years ]
    Efficacy of ME-401 assessed by complete response (CR)
  • Efficacy of ME-401 [ Time Frame: 2 years ]
    Efficacy of ME-401 assessed by minimal residual disease negativity (MRD)
  • Efficacy of ME-401 [ Time Frame: 2 years ]
    Efficacy of ME-401 assessed by progression-free survival (PFS)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma
Official Title  ICMJE 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
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
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE
  • 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)
Intervention  ICMJE
  • Drug: ME-401
    60 mg
  • Drug: Rituximab
    IV infusion 375 mg/m2
    Other Name: Rituxan
  • Drug: Zanubrutinib
    160 mg bid
Study Arms  ICMJE
  • 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.
    Intervention: Drug: ME-401
  • 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.
    Interventions:
    • Drug: ME-401
    • Drug: Rituximab
  • 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).
    Interventions:
    • Drug: ME-401
    • Drug: Zanubrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 1, 2019)
177
Original Estimated Enrollment  ICMJE
 (submitted: September 23, 2016)
84
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lisa McColley 402-238-2615 lmccolley@clinipace.com
Contact: MEI Pharma 858-369-7100 patients@meipharma.com
Listed Location Countries  ICMJE Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02914938
Other Study ID Numbers  ICMJE ME-401-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MEI Pharma, Inc.
Study Sponsor  ICMJE MEI Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MEI Pharma, Inc.
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP