Study of Lenalidomide in Combination With RICE With Lenalidomide Maintenance Post-Auto Transplant for DLBCL (RICER)
The standard of care therapy for DLBCL in the relapsed setting is RICE with the plan for the patient to proceed to transplant. This protocol will add Revlimid to the first 7 days of the RICE therapy and again after transplant as maintenance. To improve over all outcome and survival.
Hypothesis is that combining lenalidomide with standard of care (RICE) may increase overall response rate thus increasing the number of patients able to proceed with autologous stem cell transplant. This in turn may translate into improved overall survival and progression free survival.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phae I/II Study of Lenalidomide in Combination With Rituximab, Ifosfamide, Etoposide, and Carboplatin (RICER) as Salvage Therapy With Single Agent Lenalidomide as Maintenance Therapy Post-Autologous Stem Cell Transplantation for the Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) Patients in First Relapse|
- Stage 1 - Safety (type, frequency, severity and relationship of adverse events to study treatment) and tolerability [ Time Frame: overall response rate ] [ Designated as safety issue: Yes ]compare the effect of treatment with 4 weeks of high dose IFN α-2b on the relapse free survival of patients with resected melanoma
- Stage 1 - Overall response rate (CR, PR, SD) [ Time Frame: overall response rate ] [ Designated as safety issue: Yes ]
- Stage 2 - Proportion of patients with a stem cell collection of at least 3x106 CD34+ cells prior to ASCT [ Time Frame: 1 and 2 Year Progression ] [ Designated as safety issue: Yes ]Stage 2 - 1 and 2 Year Progression Free Survival (PFS)
- Stage 3 - Overall response rate (CR, PR, SD) and complete response rate, and conversion to higher quality of response during maintenance (e.g. from PR to CR) [ Time Frame: Evaluate PFS at 2 yrs post transplant ] [ Designated as safety issue: Yes ]Evaluate PFS at 2 yrs post transplant
- Stage 2 • Incidence of DLT for determination of MTD to be used in Stage II conversion to higher quality of response during maintenance (e.g. from PR to CR) [ Designated as safety issue: Yes ]
- Stage 2 - 1 and 2 Year Progression Free Survival (PFS) [ Designated as safety issue: Yes ]
- Stage 2 - 1 and 2 year Overall Survival (OS) [ Designated as safety issue: Yes ]
- Stage 2 - Proportion of patients proceeding to stem cell collection and ASCT [ Designated as safety issue: Yes ]
- Stage 2 - Treatment related adverse events [ Designated as safety issue: Yes ]
- Stage 3 - Evaluate PFS at 2 yrs post transplant [ Designated as safety issue: Yes ]
- Stage 3 - Evaluate Overall survival at 2 yrs post transplant [ Designated as safety issue: Yes ]
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||October 2013|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Cohort 1: RICE + Lenalidomide 10mg days 1-7 Cohort 2: RICE + Lenalidomide 15mg days 1-7 Cohort 3: RICE + Lenalidomide 20mg days 1-7 Cohort 4: RICE + Lenalidomide 25mg days 1-7
Lenalidomide 25mg days 1-21 every 28 days
This is a 3-Stage, phase I/II, single-arm, open-label study. The first and second stage of the study will assess the safety and efficacy of lenalidomide, rituximab, Ifosfamide, etoposide, and carboplatin (RICER) for the treatment of DLBCL patients in first relapse. The third stage of the study will assess the safety and efficacy of post-ASCT lenalidomide maintenance in patients with DLBC.
In stage I of the study, escalating doses of lenalidomide (10, 15, 20, and 25 mg daily x 7 days on Days 1-7) along with RICE therapy will be given to cohorts of subjects in a standard 3+3 design (see section 5.4.2 for dose escalation schema) until the maximum tolerated dose (MTD) has been determined.
In stage II, all subjects will be given RICE plus the MTD of lenalidomide. The starting dose of lenalidomide in Stage II will be modified for reduced renal function as outlined in Section 5.4.2.
In both stage I and stage II, subjects who have stable disease or progression of disease after 2 cycles of RICER will be taken off study. Subjects who achieve > PR to 2 cycles of RICER will receive a third cycle followed by stem cell collection and ASCT.
Each cycle is 14 days. Delays in initiating a new cycle are allowed up to 14 days for Stages I and II. The planned number of cycles is 3.
After the second cycle, restaging with PET and CT scans is performed. Patients with progressive disease are removed from the study, chemosensitive patients (CR/Cru and PR) proceed with third cycle of RICER. Stem cell collection will be completed within 10-14 days after third cycle of RICER. HDCMT-autoSCT will be performed after patient recovers from stem cell collection toxicities. HDCMT (high dose chemotherapy) followed by autologous stem cell transplant involves administration of chemotherapy with BEAM (BCNU, Etoposide, Ara-C, Melphalan) followed by infusion of autologous stem cells. Involved-field radiation to the sites of bulky disease will be allowed prior to HDCMT-SCT.
Stage III, after recovery from aSCT, but not to exceed 90 days all eligible subjects will receive lenalidomide maintenance therapy (po daily on Days 1-21 q28 days) for up to 1 year. Delays in initiating a new cycle up to 28 days are allowed in Stage III. Subjects will be followed for progression- free survival and overall survival for up to 2 years. The starting dose of lenalidomide maintenance treatment will be based on calculated creatinine clearance within 28 days prior to the start of lenalidomide maintenance
|Contact: Tatyana Feldman, MD||201-996-5900|
|Contact: Marisa L Valentinetti, RN||551-336-8073||MValentinetti@hackensackUMC.org|
|United States, New Jersey|
|John Theurer Cancer Center at Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Marisa Valentinetti, RN 551-996-8073 MValentinetti@hackensackUMC.org|
|Contact: Kara Yannotti, RN 551-996-5168 email@example.com|
|Principal Investigator: Tatyana Feldman, MD|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Peggy Alton 919-681-4769 firstname.lastname@example.org|
|Principal Investigator: Anne W. Beaven, MD|
|Principal Investigator:||Tatyana Feldman, MD||Hackensack University Medical Center|