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

Pharmacyclics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Follicular Lymphoma; Diffuse Large B-Cell Lymphoma

Treatments: Drug: MEDI4736; Drug: Ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02401048

PCYC-1136-CA

Details and patient eligibility

About

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.

Enrollment: 61 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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61 participants in 2 patient groups

Phase 1b/ 2: Follicular lymphoma expansion cohort

Experimental group

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.

Treatment:

Drug: Ibrutinib

Drug: MEDI4736

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

Experimental group

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.

Treatment:

Drug: Ibrutinib

Drug: MEDI4736