A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas

Follicular Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02401048
• Other study ID #: PCYC-1136-CA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2015
• Est. completion date: November 2017

Study information

• Verified date: June 2019
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Ibrutinib

• MEDI4736

Locations

Country	Name	City	State
United States	Site-0729	Ann Arbor	Michigan
United States	Site-0397	Birmingham	Alabama
United States	Site-0020/0173	Boston	Massachusetts
United States	Site-0126	Chicago	Illinois
United States	Site-0130	Detroit	Michigan
United States	Site-0047	Duarte	California
United States	Site-0343	Hackensack	New Jersey
United States	Site-0388	Miami	Florida
United States	Site-0402	Philadelphia	Pennsylvania
United States	Site-0114	Seattle	Washington
United States	Site-0038	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Pharmacyclics LLC.	AstraZeneca, Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b/2 : Overall Response Rate of Number of Participants	The response criteria is measured based on the revised criteria for malignant lymphoma described by the International Working Group for NHL (Cheson 2014).	From the date of first study treatment until progressive disease
Secondary	Phase 1b/ 2: Duration of Response		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.
Secondary	Phase 1b/ 2: Progression-free Survival (PFS)		first dose date of study drug (ibrutinib or MEDI4736) to the first documentation of disease progression
Secondary	Phase 1b/2: Overall Survival		First dose date of study drug (ibrutinib or MEDI4736) to the date of death due to any cause
Secondary	Phamacokinetics: Mean Maximum Observed Plasma Concentration (Cmax) for Ibrutinib	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)	Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Secondary	Pharmacokinetics: Mean Time to Maximum Observed Plasma Concentration (Tmax) for Ibrutinib	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)	Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Secondary	Pharmacokinetics: Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC0-24h) for Ibrutinib	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)	Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Secondary	Pharmacokinetics: Mean Terminal Elimination Half-Life (t1/2,Term) for Ibrutinib	Ibrutinib terminal elimination half-life associated with the terminal slope (?z) of the semi-logarithmic plasma concentration-time curve, calculated as 0.693/?z on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)	Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Secondary	Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736	Peak plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)	Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Secondary	Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736	Trough plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)	Cycle 6 Day 1 (predose)
Secondary	Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax	Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Cmax for MEDI4736	Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Secondary	Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough	Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Ctrough for MEDI4736	Cycle 6 Day 1 (predose)
Secondary	Bruton Tyrosine Kinase (BTK) Occupancy	BTK occupancy	ibrutinib Lead-in Day 6 or 7 pre-dose
Secondary	Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas	BTK occupancy	Cycle 3 Day 1 Pre-dose
Secondary	Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas	Detectable Free Serum PD-L1 level	Cycle 3 Day1 Pre-dose