- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02401048
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
June 3, 2019 updated by: Pharmacyclics LLC.
A Multi-Center Open-Label Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With MEDI4736, in Subjects With Relapsed or Refractory Lymphomas
The purpose of this study is to evaluate the efficacy, safety and tolerability of the combination treatment of ibrutinib and MEDI4736 in subjects with relapsed or refractory lymphomas.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
61
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- Site-0397
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California
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Duarte, California, United States, 91010
- Site-0047
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Stanford, California, United States, 94305
- Site-0038
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Florida
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Miami, Florida, United States, 33136
- Site-0388
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Illinois
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Chicago, Illinois, United States, 60637
- Site-0126
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Site-0020/0173
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Michigan
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Ann Arbor, Michigan, United States, 48109
- Site-0729
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Detroit, Michigan, United States, 48201
- Site-0130
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Site-0343
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Site-0402
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Washington
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Seattle, Washington, United States, 98104
- Site-0114
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Pathologically documented relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL)
- Measurable disease sites on CT scan (>1.5 cm in longest dimension)
Adequate hematologic function:
- Absolute Neutrophil Count >1500 cells/mm3
- Platelets >50000 cells/mm3
- Hemoglobin >8.0 g/dL
Adequate hepatic and renal function:
- AST or ALT ≤2.5 x ULN
- Bilirubin ≤1.5 x ULN
- Estimated creatinine clearance (Cockcroft-Gault) >40 mL/min
- ECOG 0 or 1
Exclusion Criteria:
- Received prior therapies: ibrutinib, or other BTK inhibitor and/or anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody
- Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor
- Primary CNS lymphoma or evidence of CNS involvement by lymphoma
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Phase 1b/ 2: Follicular lymphoma expansion cohort
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 explored in cohort 1 and followed a 6+3 dose de-escalation design.
Phase 2 used the phase 1b starting dose.
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EXPERIMENTAL: Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 explored in cohort 1 and followed a 6+3 dose de-escalation design.
Phase 2 used the phase 1b starting dose.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1b/2 : Overall Response Rate of Number of Participants
Time Frame: From the date of first study treatment until progressive disease
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The response criteria is measured based on the revised criteria for malignant lymphoma described by the International Working Group for NHL (Cheson 2014).
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From the date of first study treatment until progressive disease
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1b/ 2: Duration of Response
Time Frame: Time from the date of initial response to the date of disease progression or the date of death due to any cause, whichever occurs first.
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Time from the date of initial response to the date of disease progression or the date of death due to any cause, whichever occurs first.
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Phase 1b/ 2: Progression-free Survival (PFS)
Time Frame: first dose date of study drug (ibrutinib or MEDI4736) to the first documentation of disease progression
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first dose date of study drug (ibrutinib or MEDI4736) to the first documentation of disease progression
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Phase 1b/2: Overall Survival
Time Frame: First dose date of study drug (ibrutinib or MEDI4736) to the date of death due to any cause
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First dose date of study drug (ibrutinib or MEDI4736) to the date of death due to any cause
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Phamacokinetics: Mean Maximum Observed Plasma Concentration (Cmax) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Maximum observed plasma concentration of ibrutinib during the dosing interval on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
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Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Pharmacokinetics: Mean Time to Maximum Observed Plasma Concentration (Tmax) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Time to corresponding maximum observed plasma concentration of ibrutinib during the dosing interval on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
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Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Pharmacokinetics: Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC0-24h) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Ibrutinib AUC0-24h calculated using linear trapezoidal summation after dosing from time 0 to 24 hours on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
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Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Pharmacokinetics: Mean Terminal Elimination Half-Life (t1/2,Term) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Ibrutinib terminal elimination half-life associated with the terminal slope (λz) of the semi-logarithmic plasma concentration-time curve, calculated as 0.693/λz on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
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Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
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Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736
Time Frame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
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Peak plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
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Cycle 6 Day 1 (collected 10 minutes after end of infusion)
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Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736
Time Frame: Cycle 6 Day 1 (predose)
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Trough plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
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Cycle 6 Day 1 (predose)
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Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax
Time Frame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
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Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Cmax for MEDI4736
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Cycle 6 Day 1 (collected 10 minutes after end of infusion)
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Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough
Time Frame: Cycle 6 Day 1 (predose)
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Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Ctrough for MEDI4736
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Cycle 6 Day 1 (predose)
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Bruton Tyrosine Kinase (BTK) Occupancy
Time Frame: ibrutinib Lead-in Day 6 or 7 pre-dose
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BTK occupancy
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ibrutinib Lead-in Day 6 or 7 pre-dose
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Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas
Time Frame: Cycle 3 Day 1 Pre-dose
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BTK occupancy
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Cycle 3 Day 1 Pre-dose
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Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
Time Frame: Cycle 3 Day1 Pre-dose
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Detectable Free Serum PD-L1 level
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Cycle 3 Day1 Pre-dose
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Emily Liu, Pharmacyclics LLC.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2015
Primary Completion (ACTUAL)
November 1, 2017
Study Completion (ACTUAL)
November 1, 2017
Study Registration Dates
First Submitted
March 4, 2015
First Submitted That Met QC Criteria
March 23, 2015
First Posted (ESTIMATE)
March 27, 2015
Study Record Updates
Last Update Posted (ACTUAL)
June 27, 2019
Last Update Submitted That Met QC Criteria
June 3, 2019
Last Verified
June 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PCYC-1136-CA
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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