Clinical trial NCT02142049: Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Official title: A Multicenter Study of Ibrutinib and Lenalidomide in Combination With DA-EPOCH-R in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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)
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
Collaborators: name: Celgene Corporation
First posted: 2014-05-20
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Detailed 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).

Eligibility 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability
timeFrame: 1 year after last subjects received the first dose
measure: Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR
timeFrame: 1 year after last subjects received the first dose
Secondary outcomes:
measure: Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy
timeFrame: 1 year after last subjects received the first dose
measure: Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 1 year after last subjects received the first dose
measure: Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy
timeFrame: 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.
measure: Duration of Response (DOR)
timeFrame: 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.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: SITE-1
state: California
city: Los Angeles
country: United States
facility: SITE-2
state: California
city: Orange
country: United States
facility: SITE-10
state: California
city: Chicago
country: United States
facility: SITE-3
state: Illinois
city: Baltimore
country: United States
facility: SITE-5
state: Maryland
city: Bethesda
country: United States
facility: SITE-6
state: Maryland
city: Ann Arbor
country: United States
facility: SITE-4
state: Michigan
city: Albuquerque
country: United States
facility: SITE-8
state: New Mexico
city: Stony Brook
country: United States
facility: SITE-9
state: New York
city: Charleston
country: United States
facility: SITE-7
state: South Carolina
Study officials:
affiliation: Pharmacyclics LLC.
name: Jutta Neuenburg, MD
role: STUDY_DIRECTOR
References:
citation: 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.