- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02142049
Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
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 Overview
Status
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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California
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Duarte, California, United States, 91010
- SITE-1
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Los Angeles, California, United States, 90095
- SITE-2
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Orange, California, United States, 92868
- SITE-10
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Illinois
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Chicago, Illinois, United States, 60612
- SITE-3
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Maryland
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Baltimore, Maryland, United States, 21201
- SITE-5
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Bethesda, Maryland, United States, 20892
- SITE-6
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Michigan
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Ann Arbor, Michigan, United States, 48109
- SITE-4
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New Mexico
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Albuquerque, New Mexico, United States, 87106
- SITE-8
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New York
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Stony Brook, New York, United States, 11794
- SITE-9
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South Carolina
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Charleston, South Carolina, United States, 29425
- SITE-7
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1: Dose Level 1
Ibrutinib 560 mg PO + DA-EPOCH-R
|
Ibrutinib
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
|
Experimental: Part 1: Dose Level 2
Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R
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Ibrutinib
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Lenalidomide
|
Experimental: Part 1: Dose Level 3
Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R
|
Ibrutinib
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Lenalidomide
|
Experimental: Part 1: Dose Level 4
Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
|
Ibrutinib
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Lenalidomide
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Experimental: Part 2: RP2D
Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
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Ibrutinib
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Lenalidomide
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R
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1 year after last subjects received the first dose
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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
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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.
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1 year after last subjects received the first dose
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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1 year after last subjects received the first dose
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Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
Time Frame: 1 year after last subjects received the first dose
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Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.
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1 year after last subjects received the first dose
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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.
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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.
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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.
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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.
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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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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.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Jutta Neuenburg, MD, Pharmacyclics LLC (An AbbVie Company)
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Lenalidomide
Other Study ID Numbers
- PCYC-1124-CA
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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