Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Pharmacyclics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Diffuse Large B Cell Lymphoma Refractory; Diffuse Large B Cell Lymphoma Relapsed

Treatments: Drug: Ibrutinib; Drug: DA-EPOCH-R; Drug: Lenalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT02142049

PCYC-1124-CA

Details and patient eligibility

About

This is a Phase 1b/2, open-label, non-randomized multicenter study to assess the safety and efficacy of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL).

Full description

This is a Phase 1b, open-label, non-randomized multicenter study conducted in 2 parts. Part 1, will determine the MTD of the combination of ibrutinib, lenalidomide and DA-EPOCH-R in subjects with DLBCL.

Ibrutinib will be administered at a fixed dose of 560 mg and lenalidomide will be dose-escalated. DA-EPOCH-R will be given at standard doses.

For Part 2, the MTD determined in Part 1 will be the dose used for all subjects. If no MTD is identified, then subjects in Part 2 will be treated with the maximum administered doses (MAD, treatment doses from dose Level 4).

The primary objective for Part 2 is to determine the ORR of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with ABC DLBCL as analyzed by gene expression profiling when treated at recommended phase 2 dose (RP2D).

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Major inclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

• Pathologically confirmed relapsed/refractory DLBCL

• Subjects must have ≥1 measurable disease site on CT scan (≥ 1.5 cm in longest dimension).

• Adequate hepatic and renal function:

  • AST or ALT ≤2.5 x ULN
  • Serum Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥60 mL/min/1.73
  • Bilirubin ≤1.5 x ULN

• Adequate hematologic function:

  • ANC >1,000 cells/mm3
  • Platelets ≥75,000 cells/mm3
  • Hemoglobin ≥8.0 g/dL
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be ≤1.5 x the upper limit of the normal range (ULN)

• Must be registered into the Revlimid REMS™program and be willing to comply with the requirements of Revlimid REMS™.

Major Exclusion Criteria:

• Known central nervous system lymphoma
• Any chemotherapy, external beam radiation therapy, or anti-cancer antibodies within 2 weeks
• Radio- or toxin-immunoconjugates within 10 weeks
• Prior allogenetic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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35 participants in 5 patient groups

Part 1: Dose Level 1

Experimental group

Description:

Ibrutinib 560 mg PO + DA-EPOCH-R

Treatment:

Drug: Ibrutinib

Drug: DA-EPOCH-R

Part 1: Dose Level 2

Experimental group

Description:

Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R

Treatment:

Drug: Ibrutinib

Drug: DA-EPOCH-R

Drug: Lenalidomide

Part 1: Dose Level 3

Experimental group

Description:

Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R

Treatment:

Drug: Ibrutinib

Drug: DA-EPOCH-R

Drug: Lenalidomide

Part 1: Dose Level 4

Experimental group

Description:

Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R

Treatment:

Drug: Ibrutinib

Drug: DA-EPOCH-R

Drug: Lenalidomide

Part 2: RP2D

Experimental group

Description:

Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R

Treatment:

Drug: Ibrutinib

Drug: DA-EPOCH-R

Drug: Lenalidomide