Lenalidomide With or Without Idelalisib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
This Phase I/II trial studies the safety and effectiveness of lenalidomide with or without idelalisib. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Idelalisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether lenalidomide is more effective with or without idelalisib in treating mantle cell lymphoma.
Relapsed/Refractory Mantle Cell Lymphoma
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
- Overall survival (OS) (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Overall response rate (partial or complete response) (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2013|
|Estimated Primary Completion Date:||August 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|