Rituximab, Pentostatin, Cyclophosphamide, and Lenalidomide in Treating Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Number of Participants With Complete Response (CR) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

  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

  
  

• Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide [ Time Frame: 12 months ] [ Designated as safety issue: No ]

  According to the NCIWG criteria, response is defined as follows:

  nPR: Meets all criteria for CR, as described above, except the presence of residual clonal nodules in the bone marrow PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions SD: participant who does not meet any of the criteria described above

  
  
• Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells to determine if there was any MRD.
  
  
• Number of Participants Who Convert From a CR With MRD or nPR, PR, or Stable Disease With Residual Disease After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Number of Participants With a Response (CR, nPR, PR) [ Time Frame: During treatment (up to 5 years) ] [ Designated as safety issue: No ]
  Response criteria described in above outcomes
  
  
• Overall Survival (OS) [ Time Frame: time from registration to death (up to 5 years) ] [ Designated as safety issue: No ]
  Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method.
  
  
• Time to Disease Progression (TTP) [ Time Frame: time from registration to progression (up to 5 years) ] [ Designated as safety issue: No ]
  Time to disease progression (TTP) was defined as the time from registration to the earliest date documentation of disease progression. Participants were followed for a maximum of 5 years from registration. The median TTP with 95% CI was estimated using the Kaplan Meier method.
  
  
• Number of Participants With IgVH Testing at Baseline Who Also Had a Clinical Response (CR, nPR, or PR). [ Time Frame: During treatment (up to 5 years) ] [ Designated as safety issue: No ]
  Response categories described in above outcome measures. IgVH mutation status describe in baseline characteristics section.
  
  
• Number of Participants With CD38 Testing at Baseline Who Also Had a Clinical Response (CR, nPR, or PR). [ Time Frame: During treatment (up to 5 years) ] [ Designated as safety issue: No ]
  Response categories described in above outcome measures. CD38 status described in baseline characteristics section.
  
  
• Number of Participants With ZAP-70 Testing at Baseline Who Also Had a Clinical Response (CR, nPR, or PR). [ Time Frame: During treatment (up to 5 years) ] [ Designated as safety issue: No ]
  Response categories described in above outcome measures. ZAP-70 status describe in baseline characteristics section.
  
  
• Number of Participants With FISH Testing at Baseline Who Also Had a Clinical Response (CR, nPR, or PR). [ Time Frame: During treatment (up to 5 years) ] [ Designated as safety issue: No ]
  Response categories described in above outcome measures. FISH status describe in baseline characteristics section.
  
  

OBJECTIVES:

Primary

• 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 lymphocytic lymphoma.

Secondary

• 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 PCR-lenalidomide therapy.
• To use evaluation of MRD to determine the duration of lenalidomide therapy.
• To determine the progression-free survival in CLL patients using this treatment regimen.

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.