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Completed

NCT Number: NCT02401048

A Multi-Center Study of 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.

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Key information

Conditions

Diffuse Large B-cell Lymphoma Follicular Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Site-0397, Birmingham, Alabama, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ibrutinib

Drug

MEDI4736

Drug

Primary outcomes

  1. Phase 1b/2 : Overall Response Rate of Number of Participants

    Time frame: From the date of first study treatment until progressive disease

    The response criteria is measured based on the revised criteria for malignant lymphoma described by the International Working Group for NHL (Cheson 2014).

Secondary outcomes

  1. 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.

  2. 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

  3. 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

  4. 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)

    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)

  5. 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)

    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)

  6. 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)

    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)

  7. 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)

    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)

  8. Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736

    Time frame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)

    Peak plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)

  9. Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736

    Time frame: Cycle 6 Day 1 (predose)

    Trough plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)

  10. Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax

    Time frame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)

    Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Cmax for MEDI4736

  11. Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough

    Time frame: Cycle 6 Day 1 (predose)

    Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Ctrough for MEDI4736

  12. Bruton Tyrosine Kinase (BTK) Occupancy

    Time frame: ibrutinib Lead-in Day 6 or 7 pre-dose

    BTK occupancy

  13. Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas

    Time frame: Cycle 3 Day 1 Pre-dose

    BTK occupancy

  14. Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas

    Time frame: Cycle 3 Day1 Pre-dose

    Detectable Free Serum PD-L1 level

Sponsors and collaborators

Lead sponsor

Pharmacyclics LLC.

Industry

Collaborators

  • AstraZeneca
  • Janssen Research & Development, LLC

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Mar 27, 2015
Registry last updated
Jun 27, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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