Clinical trial NCT02401048: A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Follicular Lymphoma
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
name: Janssen Research & Development, LLC
First posted: 2015-03-27
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Absolute Neutrophil Count \>1500 cells/mm3
  2. Platelets \>50000 cells/mm3
  3. Hemoglobin \>8.0 g/dL
* Adequate hepatic and renal function:

  1. AST or ALT ≤2.5 x ULN
  2. Bilirubin ≤1.5 x ULN
  3. 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

Primary outcomes:
measure: Phase 1b/2 : Overall Response Rate of Number of Participants
timeFrame: From the date of first study treatment until progressive disease
Secondary outcomes:
measure: Phase 1b/ 2: Duration of Response
timeFrame: 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.
measure: Phase 1b/ 2: Progression-free Survival (PFS)
timeFrame: first dose date of study drug (ibrutinib or MEDI4736) to the first documentation of disease progression
measure: Phase 1b/2: Overall Survival
timeFrame: First dose date of study drug (ibrutinib or MEDI4736) to the date of death due to any cause
measure: Phamacokinetics: Mean Maximum Observed Plasma Concentration (Cmax) for Ibrutinib
timeFrame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
measure: Pharmacokinetics: Mean Time to Maximum Observed Plasma Concentration (Tmax) for Ibrutinib
timeFrame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
measure: Pharmacokinetics: Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC0-24h) for Ibrutinib
timeFrame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
measure: Pharmacokinetics: Mean Terminal Elimination Half-Life (t1/2,Term) for Ibrutinib
timeFrame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
measure: Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736
timeFrame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
measure: Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736
timeFrame: Cycle 6 Day 1 (predose)
measure: Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax
timeFrame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
measure: Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough
timeFrame: Cycle 6 Day 1 (predose)
measure: Bruton Tyrosine Kinase (BTK) Occupancy
timeFrame: ibrutinib Lead-in Day 6 or 7 pre-dose
measure: Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas
timeFrame: Cycle 3 Day 1 Pre-dose
measure: Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
timeFrame: Cycle 3 Day1 Pre-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site-0397
state: Alabama
city: Duarte
country: United States
facility: Site-0047
state: California
city: Stanford
country: United States
facility: Site-0038
state: California
city: Miami
country: United States
facility: Site-0388
state: Florida
city: Chicago
country: United States
facility: Site-0126
state: Illinois
city: Boston
country: United States
facility: Site-0020/0173
state: Massachusetts
city: Ann Arbor
country: United States
facility: Site-0729
state: Michigan
city: Detroit
country: United States
facility: Site-0130
state: Michigan
city: Hackensack
country: United States
facility: Site-0343
state: New Jersey
city: Philadelphia
country: United States
facility: Site-0402
state: Pennsylvania
city: Seattle
country: United States
facility: Site-0114
state: Washington
Study officials:
affiliation: Pharmacyclics LLC.
name: Emily Liu
role: STUDY_DIRECTOR
References: