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NCT Number: NCT02142049

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

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).

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Key information

Conditions

Diffuse Large B Cell Lymphoma Relapsed Diffuse Large B Cell Lymphoma Refractory Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

SITE-1, Duarte, California, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ibrutinib

Drug

Ibrutinib

DA-EPOCH-R

Drug

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

Lenalidomide

Drug

Lenalidomide

Primary outcomes

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

    Time frame: 1 year after last subjects received the first dose

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

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

    Time frame: 1 year after last subjects received the first dose

    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.

Secondary outcomes

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

    Time frame: 1 year after last subjects received the first dose

    Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator.

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

    Time frame: 1 year after last subjects received the first dose

    Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.

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

    Time frame: 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.

    Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause. OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology.

  4. Duration of Response (DOR)

    Time frame: 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.

    Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented.

Sponsors and collaborators

Lead sponsor

Pharmacyclics LLC.

Industry

Collaborators

  • Celgene Corporation

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
May 20, 2014
Registry last updated
Feb 5, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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