Study Stopped
discontinuation of zandelisib program
A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma
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
1 other identifier
interventional
97
2 countries
24
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2016
Longer than P75 for phase_1
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 12, 2016
CompletedFirst Posted
Study publicly available on registry
September 26, 2016
CompletedStudy Start
First participant enrolled
October 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 29, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
March 29, 2023
CompletedMay 9, 2023
December 1, 2022
6.5 years
September 12, 2016
May 5, 2023
Conditions
Outcome Measures
Primary Outcomes (7)
Minimum Biologically Effective Dose (mBED) of ME-401 alone
The mBED will be defined as the dose that is safe and that achieves an objective response rate that is not less than 30%.
1 year
Maximally Tolerated Dose (MTD) of ME-401 alone
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
1 year
Dose Limiting Toxicities (DLTs) of ME-401 alone
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
within the first 56 days
Evaluate the safety and tolerability of ME-401 plus rituximab
Safety and tolerability will be measured by the number of treatment related AEs
1 year
Determine the MTD of ME-401 plus zanubrutinib
The MTD of ME-401 is defined as the dose level with a DLT rate closest to 0.25.
1 year
Determine the DLTs of ME-401 plus zanubrutinib
DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 plus zanubrutinib
within the first 56 days
Evaluate the safety and tolerability of ME-401 plus zanubrutinib
Safety and tolerability will be measured by the number of treatment related AEs
1 year
Secondary Outcomes (10)
Safety profile of ME-401 alone
1 year
Efficacy of ME-401 alone as assessed by (OR)
2 years
Evaluate the (AUC) PK of ME-401 alone
2 years
Evaluate the PK (Cmax) of ME-401 alone
2 years
Efficacy of ME-401 with rituximab
2 years
- +5 more secondary outcomes
Study Arms (3)
ME-401 Alone
EXPERIMENTALThis 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 in Combination with Rituximab
EXPERIMENTALThe 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 in Combination with Zanubrutinib
EXPERIMENTALThe 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).
Interventions
60 mg
Eligibility Criteria
You may qualify if:
- 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
- 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)
- +13 more criteria
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MEI Pharma, Inc.lead
Study Sites (24)
University of Arizona
Tucson, Arizona, 85724, United States
Compassionate Care
Corona, California, 92708, United States
Sylvester Comprehensive Cancer Center (Univ of Miami School of Med)
Miami, Florida, 33136, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana Farber
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering
Commack, New York, 11725, United States
Memorial Sloan Kettering
Harrison, New York, 10604, United States
NYU Langone Laura & Isaac - Perlmutter Cancer Center
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Stony Brook
Stony Brook, New York, 11794, United States
Memorial Sloan Kettering
Uniondale, New York, 11553, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Vanderbilt
Nashville, Tennessee, 37240, United States
University of Southwestern Medical Center
Dallas, Texas, 75390, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Swedish Cancer Institute
Edmonds, Washington, 98026, United States
Swedish Cancer Institute
Issaquah, Washington, 98029, United States
Swedish Cancer Center
Seattle, Washington, 98104, United States
Carbone Cancer Center
Madison, Wisconsin, 53792, United States
lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH
Bellinzona, Switzerland
Related Publications (1)
Pagel JM, Soumerai JD, Reddy N, Jagadeesh D, Stathis A, Asch A, Salman H, Kenkre VP, Iasonos A, Llorin-Sangalang J, Li J, Zelenetz AD. Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial. Lancet Oncol. 2022 Aug;23(8):1021-1030. doi: 10.1016/S1470-2045(22)00333-3. Epub 2022 Jul 11.
PMID: 35835137DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 12, 2016
First Posted
September 26, 2016
Study Start
October 1, 2016
Primary Completion
March 29, 2023
Study Completion
March 29, 2023
Last Updated
May 9, 2023
Record last verified: 2022-12