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

Diffuse Large B Cell Lymphoma Refractory Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02142049
• Other study ID #: PCYC-1124-CA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2014
• Est. completion date: August 2017

Study information

• Verified date: May 2018
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma Refractory
• Diffuse Large B Cell Lymphoma Relapsed
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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

Locations

Country	Name	City	State
United States	SITE-8	Albuquerque	New Mexico
United States	SITE-4	Ann Arbor	Michigan
United States	SITE-5	Baltimore	Maryland
United States	SITE-6	Bethesda	Maryland
United States	SITE-7	Charleston	South Carolina
United States	SITE-3	Chicago	Illinois
United States	SITE-1	Duarte	California
United States	SITE-2	Los Angeles	California
United States	SITE-10	Orange	California
United States	SITE-9	Stony Brook	New York

Sponsors (2)

Lead Sponsor	Collaborator
Pharmacyclics LLC.	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability	Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R	1 year after last subjects received the first dose
Primary	Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR	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.	1 year after last subjects received the first dose
Secondary	Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy	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.	1 year after last subjects received the first dose
Secondary	Number of Subjects With Adverse Events as a Measure of Safety and Tolerability	Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.	1 year after last subjects received the first dose
Secondary	Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy	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.	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.
Secondary	Duration of Response (DOR)	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.	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.