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

NCT02142049 | Completed Phase 1 Results

• 1 other identifier: PCYC-1124-CA
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 10

Brief Summary

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).

Conditions

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

Keywords

DLBCL; ABC; GCB; Primary Mediastinal B-cell lymphoma; Pharmacyclics; Lenalidomide; lymphoma; Rituximab; EPOCH; Recommended Phase 2 Dose(RP2D)

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability

  Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R

  1 year after last subjects received the first dose

• Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR

  Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator.

  1 year after last subjects received the first dose

Secondary Outcomes (4)

• Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy

  1 year after last subjects received the first dose

• Number of Subjects With Adverse Events as a Measure of Safety and Tolerability

  1 year after last subjects received the first dose

• Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy

  From initial dose date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose, up to 36 months at the most.

• Duration of Response (DOR)

  From initial response date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose.

Study Arms (5)

Part 1: Dose Level 1

EXPERIMENTAL

Ibrutinib 560 mg PO + DA-EPOCH-R

Drug: Ibrutinib; Drug: DA-EPOCH-R

Part 1: Dose Level 2

EXPERIMENTAL

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

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

Part 1: Dose Level 3

EXPERIMENTAL

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

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

Part 1: Dose Level 4

EXPERIMENTAL

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

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

Part 2: RP2D

EXPERIMENTAL

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

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

Interventions

Ibrutinib DRUG

Ibrutinib

Part 1: Dose Level 1; Part 1: Dose Level 2; Part 1: Dose Level 3; Part 1: Dose Level 4; Part 2: RP2D

DA-EPOCH-R DRUG

Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Part 1: Dose Level 1; Part 1: Dose Level 2; Part 1: Dose Level 3; Part 1: Dose Level 4; Part 2: RP2D

Lenalidomide DRUG

Lenalidomide

Part 1: Dose Level 2; Part 1: Dose Level 3; Part 1: Dose Level 4; Part 2: RP2D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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™.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pharmacyclics LLC.: lead
• Celgene Corporation: collaborator

Study Sites (10)

SITE-1

Duarte, California, 91010, United States

Location

SITE-2

Los Angeles, California, 90095, United States

Location

SITE-10

Orange, California, 92868, United States

Location

SITE-3

Chicago, Illinois, 60612, United States

Location

SITE-5

Baltimore, Maryland, 21201, United States

Location

SITE-6

Bethesda, Maryland, 20892, United States

Location

SITE-4

Ann Arbor, Michigan, 48109, United States

Location

SITE-8

Albuquerque, New Mexico, 87106, United States

Location

SITE-9

Stony Brook, New York, 11794, United States

Location

SITE-7

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Wilson WH, Phillips T, Popplewell L, de Vos S, Chhabra S, Kimball AS, Beaupre D, Huang DW, Wright G, Kwei K, Ping J, Neuenburg JK, Staudt LM. Phase 1b/2 study of ibrutinib and lenalidomide with dose-adjusted EPOCH-R in patients with relapsed/refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2021 Sep;62(9):2094-2106. doi: 10.1080/10428194.2021.1907371. Epub 2021 Apr 15.

  PMID: 33856277 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

ibrutinib; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Pharmacyclics, LLC

Clinical_Directors@pcyc.com

408-774-0330

Study Officials

• Jutta Neuenburg, MD

  Pharmacyclics LLC.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2014
• First Posted: May 20, 2014
• Study Start: May 1, 2014
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: February 5, 2019
• Results First Posted: February 5, 2019

Record last verified: 2018-05

Locations

US (10)