Lenalidomide With or Without Idelalisib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
|Relapsed/Refractory Mantle Cell Lymphoma||Drug: lenalidomide Drug: idelalisib||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I/Randomized Phase II Trial of Idelalisib and Lenalidomide in Patients With Relapsed/Refractory Mantle Cell Lymphoma|
- Maximum tolerated dose (MTD) of idelalisib and lenalidomide, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: 28 days ]
- Progression Free Survival (PFS) of the combination of lenalidomide, with or without idelalisib (Phase II) [ Time Frame: Time between registration and disease progression or death, assessed up to 2 years ]
- Overall survival (OS) (Phase II) [ Time Frame: Up to 2 years ]
- Overall response rate (partial or complete response) (Phase II) [ Time Frame: Up to 2 years ]
|Study Start Date:||July 2013|
|Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
Active Comparator: lenalidomide (Phase II)
Lenalidomide will be administered orally at 20 mg daily on days 1-21, repeated every 28 days for a maximum of 12 cycles (48 weeks). (Phase II)
Experimental: lenalidomide and idelalisib (Phase II)
Lenalidomide will be administered orally and daily on days 1-21, repeated every 28 days for a maximum of 12 cycles (48 weeks). Idelalisib will be orally administered for continuous 28-day cycles until progression, intolerance, or patient/physician discretion. Dosing will be determined by the Phase I portion of the study. (Phase II)
given PODrug: idelalisib
A notice of temporary accrual suspension for Alliance A051201 was issued on 1/28/14. The study was suspended to new patient accrual until a protocol amendment was finalized, which provided revised treatment instructions. The study was reactivated on 4/22/14 including the removal of the rituximab treatment arm.
Outline: This is a phase I, dose-escalation study followed by a phase II study.
The phase I treatment plan includes the following:
Lenalidomide will be tested at sequential dose levels in a standard 3+3 design.
- Dose Level 0 = 15mg/day for days 1-21 every 28 days
- Dose Level 1 = 20mg/day for days 1-21 every 28 days and
- Dose Level 2 = 25mg/day for days 1-21 every 28 days.
Patients can continue lenalidomide for up to 48 weeks (12 cycles) of treatment.
- Idelalisib will be orally administered starting at 150 mg twice daily for continuous 28-day cycles until progression, intolerance, or patient/physician discretion. The dose is the same in dose levels 0, 1, and 2.
Patients are randomized to 1 of 2 treatment arms in the Phase II treatment plan. The primary and secondary objectives for this study are:
- Phase I Primary Objective: To determine the safety and tolerability of the combination of lenalidomide with idelalisib in sequential dose cohorts.
- Phase II Primary Objective: To determine the progression-free survival (PFS) of the combination of lenalidomide with or without idelalisib in a randomized phase II design.
Phase II Secondary Objectives:
- To determine the overall response rate (ORR), complete response rate (CR), and overall survival (OS) of the combination of lenalidomide with or without idelalisib in a randomized phase II design.
- To determine the prognostic and/or predictive significance of proliferation markers and cell cycle components in patients with relapsed/refractory mantle cell lymphoma (MCL) treated with idelalisib and lenalidomide.
- To determine whether phosphorylated protein kinase B (pAKT) expression levels are correlated with response to idelalisib plus lenalidomide.
- To determine whether Notch activation as assessed by notch homolog 1, translocation- association (NOTCH1) intracellular domain (ICD) immunohistochemistry (IHC) correlates with NOTCH1 mutational status and outcome in MCL patients treated with idelalisib and lenalidomide.
- To determine whether sex determining region Y-box 11 (SOX11) expression correlates with response in patients with relapsed/refractory MCL treated with idelalisib and lenalidomide.
- To correlate cereblon (CRBN) expression with response in patients with relapsed/refractory MCL treated with idelalisib and lenalidomide.
- To evaluate several plasma cytokines and correlate observed changes to objective response rates.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01838434
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Study Chair:||Sonali Smith, MD||University of Chicago|