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 |
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Recruitment Status :
Recruiting
First Posted : September 26, 2016
Last Update Posted : August 6, 2020
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Sponsor:
MEI Pharma, Inc.
Information provided by (Responsible Party):
MEI Pharma, Inc.
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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 |
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 : | 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
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: ME-401
60 mg |
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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.
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Drug: ME-401
60 mg Drug: Rituximab IV infusion 375 mg/m2
Other Name: Rituxan |
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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 stage (up to 74 subjects).
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Drug: ME-401
60 mg Drug: Zanubrutinib 80 and 160 mg bid |
Primary Outcome Measures :
- 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 56 days ]DLTs will be measured by the number of treatment related AEs that occur within the first 56 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
Secondary Outcome Measures :
- 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)
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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
- Subjects with CLL/SLL must have prior treatment with BTK inhibitor and must have had progression or recurrence while on treatment of within 12 mos from BTK treatment
- 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)
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: MEI Pharma | 858-369-7100 | patients@meipharma.com |
Locations
Show 21 study locations
Sponsors and Collaborators
MEI Pharma, Inc.
| Responsible Party: | MEI Pharma, Inc. |
| ClinicalTrials.gov Identifier: | NCT02914938 |
| Other Study ID Numbers: |
ME-401-002 |
| First Posted: | September 26, 2016 Key Record Dates |
| Last Update Posted: | August 6, 2020 |
| Last Verified: | December 2019 |
Additional relevant MeSH terms:
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Lymphoma Lymphoma, Non-Hodgkin 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, Lymphoid 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 |