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
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
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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Stage 1 - Safety (type, frequency, severity and relationship of adverse events to study treatment) and tolerability
compare the effect of treatment with 4 weeks of high dose IFN α-2b on the relapse free survival of patients with resected melanoma
overall response rate
Tatyana Feldman, MD
Hackensack University Medical Center
United States: Food and Drug Administration
|Duke University Medical Center||Durham, North Carolina 27710|
|John Theurer Cancer Center at Hackensack University Medical Center||Hackensack, New Jersey 07601|