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

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ClinicalTrials.gov Identifier: NCT02142049
Recruitment Status : Completed
First Posted : May 20, 2014
Results First Posted : February 5, 2019
Last Update Posted : February 5, 2019
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Pharmacyclics LLC.

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).

Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma Relapsed Diffuse Large B Cell Lymphoma Refractory Drug: Ibrutinib Drug: DA-EPOCH-R Drug: Lenalidomide Phase 1 Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2014
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017


Arm Intervention/treatment
Experimental: Part 1: Dose Level 1
Ibrutinib 560 mg PO + DA-EPOCH-R
Drug: Ibrutinib
Ibrutinib

Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Experimental: Part 1: Dose Level 2
Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R
Drug: Ibrutinib
Ibrutinib

Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Drug: Lenalidomide
Lenalidomide

Experimental: Part 1: Dose Level 3
Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R
Drug: Ibrutinib
Ibrutinib

Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Drug: Lenalidomide
Lenalidomide

Experimental: Part 1: Dose Level 4
Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
Drug: Ibrutinib
Ibrutinib

Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Drug: Lenalidomide
Lenalidomide

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

Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim

Drug: Lenalidomide
Lenalidomide




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02142049


Locations
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United States, California
SITE-1
Duarte, California, United States, 91010
SITE-2
Los Angeles, California, United States, 90095
SITE-10
Orange, California, United States, 92868
United States, Illinois
SITE-3
Chicago, Illinois, United States, 60612
United States, Maryland
SITE-5
Baltimore, Maryland, United States, 21201
SITE-6
Bethesda, Maryland, United States, 20892
United States, Michigan
SITE-4
Ann Arbor, Michigan, United States, 48109
United States, New Mexico
SITE-8
Albuquerque, New Mexico, United States, 87106
United States, New York
SITE-9
Stony Brook, New York, United States, 11794
United States, South Carolina
SITE-7
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Pharmacyclics LLC.
Celgene Corporation
Investigators
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Study Director: Jutta Neuenburg, MD Pharmacyclics LLC an AbbVie Company
  Study Documents (Full-Text)

Documents provided by Pharmacyclics LLC.:
Study Protocol  [PDF] September 30, 2014
Statistical Analysis Plan  [PDF] September 29, 2017


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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02142049     History of Changes
Other Study ID Numbers: PCYC-1124-CA
First Posted: May 20, 2014    Key Record Dates
Results First Posted: February 5, 2019
Last Update Posted: February 5, 2019
Last Verified: May 2018

Keywords provided by Pharmacyclics LLC.:
DLBCL
ABC
GCB
Primary Mediastinal B-cell lymphoma
Pharmacyclics
Lenalidomide
lymphoma
Rituximab
EPOCH
Recommended Phase 2 Dose(RP2D)

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lenalidomide
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Prednisone
Vincristine
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists