Trial record 2 of 14 for:    DA-EPOCH +/- Rituximab: Lymphoma

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Pharmacyclics
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT02142049
First received: May 12, 2014
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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). This study is conducted in 2 parts where treatment will be administered in 3-week (21-day) cycles for 6 cycles. A standard 3+3 design will be employed in Part 1 to determine the maximum tolerated dose (MTD), which will then define the dose to be used in Part 2.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • Number of Dose-Limiting Toxicities as a Measure of Safety and Tolerability [ Time Frame: 1 year from first patient's first dose ] [ Designated as safety issue: Yes ]
    Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R

  • Number of Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy [ Time Frame: 1 year after last patient's first dose ] [ Designated as safety issue: No ]
    Part 2 - Overall Response rate will be 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.


Secondary Outcome Measures:
  • Number of Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy [ Time Frame: 1 year after first patient's first dose ] [ Designated as safety issue: No ]
    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.

  • Number of Patients with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 year after last patient's first dose ] [ Designated as safety issue: Yes ]
    Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.

  • Duration of Response (DOR), Progression Free Survival (PRF) and Overall Survival (OS) as a Measure of Efficacy [ Time Frame: 1 year after firs patient's last dose ] [ Designated as safety issue: No ]

    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.

    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.



Estimated Enrollment: 56
Study Start Date: May 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Dose Level 1
Ibrutinib 560 mg PO + DA-EPOCH-R
Drug: Ibrutinib, DA-EPOCH-R
Other Name: Etoposide, Prednisone, Doxorubicin, Cyclophsosphamide, Vincristine, Rituximab, Pegfilgrastim
Experimental: Part 1: Dose Level 2
Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R
Drug: Ibrutinib, Lenalidomide, DA-EPOCH-R
Other Name: Etoposide, Prednisone, Doxorubicin, Cyclophsosphamide, Vincristine, Rituximab, Pegfilgrastim
Experimental: Part 1: Dose Level 3
Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R
Drug: Ibrutinib, Lenalidomide, DA-EPOCH-R
Other Name: Etoposide, Prednisone, Doxorubicin, Cyclophsosphamide, Vincristine, Rituximab, Pegfilgrastim
Experimental: Part 1: Dose Level 4
Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
Drug: Ibrutinib, Lenalidomide, DA-EPOCH-R
Other Name: Etoposide, Prednisone, Doxorubicin, Cyclophsosphamide, Vincristine, Rituximab, Pegfilgrastim
Experimental: Part 2: Dose Level MTD
Ibrutinib 560 mg (PO) +lenalidomide at Maximum Tolerated Dose (PO) + DA-EPOCH-R
Drug: Ibrutinib, Lenalidomide, DA-EPOCH-R
Other Name: Etoposide, Prednisone, Doxorubicin, Cyclophsosphamide, Vincristine, Rituximab, Pegfilgrastim

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 or 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02142049

Contacts
Contact: Davina Moussa 855-427-8846 medinfo@pcyc.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
UCLA Recruiting
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Pharmacyclics
Celgene Corporation
Investigators
Study Director: Jutta K. Neuenburg, MD, PhD Pharmacyclics
  More Information

No publications provided

Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT02142049     History of Changes
Other Study ID Numbers: PCYC-1124-CA
Study First Received: May 12, 2014
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pharmacyclics:
DLBCL
ABC
GCB
Primary Mediastinal B-cell lymphoma
Pharmacyclics
Lenalidomide
lymphoma
Rituximab
EPOCH

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Rituximab
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Etoposide
Lenalidomide
Prednisone
Vincristine
Thalidomide
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 31, 2014