search
Back to results

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

Primary Purpose

Diffuse Large B-Cell Lymphoma, Follicular Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ibrutinib
MEDI4736
Sponsored by
Pharmacyclics LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Site-0397
  • Site-0047
  • Site-0038
  • Site-0388
  • Site-0126
  • Site-0020/0173
  • Site-0729
  • Site-0130
  • Site-0343
  • Site-0402
  • Site-0114

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1b/ 2: Follicular lymphoma expansion cohort

Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Phase 1b/ 2: Duration of Response
Phase 1b/ 2: Progression-free Survival (PFS)
Phase 1b/2: Overall Survival
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)
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)
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)
Pharmacokinetics: Mean Terminal Elimination Half-Life (t1/2,Term) for Ibrutinib
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)
Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736
Peak plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736
Trough plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Cmax for MEDI4736
Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Ctrough for MEDI4736
Bruton Tyrosine Kinase (BTK) Occupancy
BTK occupancy
Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas
BTK occupancy
Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
Detectable Free Serum PD-L1 level

Full Information

First Posted
March 4, 2015
Last Updated
June 3, 2019
Sponsor
Pharmacyclics LLC.
Collaborators
AstraZeneca, Janssen Research & Development, LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT02401048
Brief Title
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

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
Collaborators
AstraZeneca, Janssen Research & Development, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma, Follicular Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b/ 2: Follicular lymphoma expansion cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Intervention Type
Drug
Intervention Name(s)
MEDI4736
Primary Outcome Measure Information:
Title
Phase 1b/2 : Overall Response Rate of Number of Participants
Description
The response criteria is measured based on the revised criteria for malignant lymphoma described by the International Working Group for NHL (Cheson 2014).
Time Frame
From the date of first study treatment until progressive disease
Secondary Outcome Measure Information:
Title
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.
Title
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
Title
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
Title
Phamacokinetics: Mean Maximum Observed Plasma Concentration (Cmax) for Ibrutinib
Description
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)
Time Frame
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Title
Pharmacokinetics: Mean Time to Maximum Observed Plasma Concentration (Tmax) for Ibrutinib
Description
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)
Time Frame
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Title
Pharmacokinetics: Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC0-24h) for Ibrutinib
Description
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)
Time Frame
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Title
Pharmacokinetics: Mean Terminal Elimination Half-Life (t1/2,Term) for Ibrutinib
Description
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)
Time Frame
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Title
Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736
Description
Peak plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Time Frame
Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Title
Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736
Description
Trough plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Time Frame
Cycle 6 Day 1 (predose)
Title
Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax
Description
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Cmax for MEDI4736
Time Frame
Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Title
Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough
Description
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Ctrough for MEDI4736
Time Frame
Cycle 6 Day 1 (predose)
Title
Bruton Tyrosine Kinase (BTK) Occupancy
Description
BTK occupancy
Time Frame
ibrutinib Lead-in Day 6 or 7 pre-dose
Title
Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas
Description
BTK occupancy
Time Frame
Cycle 3 Day 1 Pre-dose
Title
Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
Description
Detectable Free Serum PD-L1 level
Time Frame
Cycle 3 Day1 Pre-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emily Liu
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Site-0397
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Site-0047
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Site-0038
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Site-0388
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Site-0126
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Site-0020/0173
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Site-0729
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Site-0130
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Site-0343
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Site-0402
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Site-0114
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs