Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab Followed by Consolidation With Lenalidomide for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
- To assess the rate of complete and overall response using pentostatin,
cyclophosphamide, and rituximab (PCR) followed by consolidation with lenalidomide in
patients with previously untreated B-cell chronic lymphocytic leukemia (CLL) or small
- To assess the proportion of patients who convert from a nodular partial response (nPR),
PR, or stable disease after completing PCR to a complete response (CR) after 6 cycles
of consolidation with lenalidomide.
- To assess the proportion of patients who convert from a CR with detectable minimal
residual disease (MRD) after PCR to a CR with MRD negative state after 6 courses of
consolidation with lenalidomide.
- To assess the proportion of patients who convert from a CR with detectable MRD, nPR,
PR, or stable disease with residual disease after PCR to a CR with MRD negative state
after 6 cycles of consolidation with lenalidomide.
- To monitor and assess toxicity of this regimen.
- To determine if molecular prognostic parameters (e.g., ZAP-70, CD38, cytogenetic
abnormalities identified by FISH, IgVH mutation status) relate to response to
- To use evaluation of MRD to determine the duration of lenalidomide therapy.
- To determine the progression-free survival in CLL patients using this treatment
OUTLINE: This is a multicenter study.
- Induction therapy: Patients receive rituximab IV over 4 hours on days 1 and 2 of course
1, and over 1 hour on day 1 of each subsequent course. Patients also receive
pentostatin IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 1, and
pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for up to 6
courses in the absence of disease progression or unacceptable toxicity.
- Consolidation therapy: Beginning 2 months after completion of induction therapy,
patients receive oral lenalidomide once daily on days 1-28. Treatment repeats every 28
days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Continuation therapy: Patients with residual disease continue to receive lenalidomide
as in consolidation therapy until they achieve a minimal residual disease-negative
status or complete remission. Patients who achieve complete response with no detectable
disease discontinue therapy and enter the observation phase.
Blood samples are collected periodically during treatment for translational and
pharmacologic studies. Samples are analyzed for immunoglobulin heavy chain gene mutational
status, ZAP-70 status, and levels of VEGF, bFGF, thrombospondin, and TGF-beta by ELISA; and
for the effects of therapy on immune function. Samples are also stored for future research.
Bone marrow aspirate samples are analyzed for minimal residual disease by flow cytometry.
After completion of study treatment, patients are followed every 90 days for 3 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Complete Response (CR)
A complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months: - CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy
Tait D. Shanafelt, MD
United States: Food and Drug Administration
|Mayo Clinic Scottsdale||Scottsdale, Arizona 85259|
|Mayo Clinic - Jacksonville||Jacksonville, Florida 32224|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|