Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Durvalumab

Ibrutinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

MEDI4736

Emily Liu

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.

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

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

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 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)

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)

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)

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

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

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

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

AstraZeneca

Janssen Research & Development, LLC

Pharmacyclics LLC.

All subjects who received at least one dose of study treatment.

Phase 1b/2: Follicular Lymphoma Expansion Cohort:

Phase 1b/ 2: Diffuse Large B-cell Lymphoma Expansion Cohort:

All participants who received at least one dose of study treatment.

Phase 1b/2: Diffuse Large B-cell Lymphoma Expansion Cohort:

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Phase 1b/ 2: Follicular Lymphoma Expansion Cohort

Phase 1b/ 2: Diffuse Large B-cell Lymphoma Expansion Cohort

While the study include Phase 1b and 2, the dosing was not changed between phases (following the study design because there were no DLTs and thus no dose adjustments in from Phase 1b to Phase 2). Thus the study data were reported with Phases 1b and 2 combined.

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

Phase 1b/ 2: Duration of Response

Phase 1b/ 2: Progression-free Survival (PFS)

Phase 1b/2: Overall Survival

Lead-In Day 6/7

Cycle 3 Day 1

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data.

All subjects who received at least one dose of study treatment and had evaluable pharmacokinetic data.

Phamacokinetics: Mean Maximum Observed Plasma Concentration (Cmax) for Ibrutinib

Pharmacokinetics: Mean Time to Maximum Observed Plasma Concentration (Tmax) for Ibrutinib

Pharmacokinetics: Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC0-24h) for Ibrutinib

Pharmacokinetics: Mean Terminal Elimination Half-Life (t1/2,Term) for Ibrutinib

Phase 1b/ 2: Follicular Lymphoma & DLBCL Expansion Cohort

All subjects who received at least one dose of study treatment and had evaluable pharmacokinetic data. Result data for both cohorts was pre-specified to be combined, and was not reported separately.

Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736

Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736

Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax

Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough

All participants who received at least one dose of study treatment and had evaluable pharmacodynamics data.

Bruton Tyrosine Kinase (BTK) Occupancy

Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas

In Follicular lymphoma expansion cohort, 7 subjects are below limit of quantitation. In Diffuse large B-cell lymphoma expansion cohort, all subjects below limit of quantitation.

Spots Global Cancer Trial Database for A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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