Clinical Trials /

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

NCT02914938

Description:

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

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Follicular Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ME-401-002
  • NCT ID: NCT02914938

Conditions

  • 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)

Interventions

DrugSynonymsArms
ME-401ME-401 Alone
RituximabRituxanME-401 in Combination with Rituximab
ZanubrutinibME-401 in Combination with Zanubrutinib

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
ME-401 AloneExperimentalThis 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.
  • ME-401
ME-401 in Combination with RituximabExperimentalThe 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.
  • ME-401
  • Rituximab
ME-401 in Combination with ZanubrutinibExperimentalThe 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).
  • ME-401
  • Zanubrutinib

Eligibility 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Minimum Biologically Effective Dose (mBED) of ME-401 alone
Time Frame:1 year
Safety Issue:
Description:The mBED will be defined as the dose that is safe and that achieves an objective response rate that is not less than 30%.

Secondary Outcome Measures

Measure:Safety profile of ME-401 alone
Time Frame:1 year
Safety Issue:
Description:Safety profile will be measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measure:Efficacy of ME-401 alone as assessed by (OR)
Time Frame:2 years
Safety Issue:
Description: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).
Measure:Evaluate the (AUC) PK of ME-401 alone
Time Frame:2 years
Safety Issue:
Description:Determined by the Area Under the Concentration time curve (AUC)
Measure:Evaluate the PK (Cmax) of ME-401 alone
Time Frame:2 years
Safety Issue:
Description:Determined by Peak Plasma Concentration (Cmax)
Measure:Efficacy of ME-401 with rituximab
Time Frame:2 years
Safety Issue:
Description: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)
Measure:Evaluate the PK (AUC) of ME-401 with rituximab
Time Frame:2 years
Safety Issue:
Description:Determined by the Area Under the Concentration time curve (AUC)
Measure:Evaluate the PK (Cmax) of ME-401 with rituximab
Time Frame:2 years
Safety Issue:
Description:Determined by Peak Plasma Concentration (Cmax)
Measure:Efficacy of ME-401 with zanubrutinib
Time Frame:2 years
Safety Issue:
Description: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)
Measure:Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib
Time Frame:2 years
Safety Issue:
Description:Determined by the Area Under the Concentration time curve (AUC)
Measure:Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib
Time Frame:2 years
Safety Issue:
Description:Determined by Peak Plasma Concentration (Cmax)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MEI Pharma, Inc.

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