Fludarabine, Rituximab, and Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia

• Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab [ Time Frame: Duration of treatment (up to 13.5 months) ] [ Designated as safety issue: No ]

  A complete response, as defined by the National Cancer Institute Working Group (NCIWG):

  - CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy

  
  

• Number of Participants With a Complete or Partial Response After Induction Therapy With Fludarabine & Rituximab [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]

  Response, as defined by the National Cancer Institute Working Group (NCIWG):

  CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy

  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, >100,000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions

  
  
• 2 Year Progression Free Survival [ Time Frame: 2 years from registration ] [ Designated as safety issue: No ]
  Percentage of patients who were alive and progression free at 2 years. The 2-year progression free survival was estimated using the Kaplan Meier method.
  
  
• 2 Year Survival [ Time Frame: 2 years from registration ] [ Designated as safety issue: No ]
  Percentage of participants who were alive at 2 years. The 2 year survival was estimated using the Kaplan Meier method.
  
  
• Number of Participants With Severe Non-Hematologic Adverse Events During Treatment With Alemtuzumab [ Time Frame: 6 weeks beginning at study week 36 ] [ Designated as safety issue: Yes ]

  The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0 was used to evaluate toxicity. Severe Adverse events are defined as grade 3, 4 or 5, at least possibly related to treatment.

  Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.

  
  

PRIMARY OBJECTIVES:

I. To determine the rate of complete response and toxicity of concurrent treatment with fludarabine and rituximab followed by consolidative alemtuzumab in patients with previously untreated, but symptomatic, CLL.

II. To determine if alemtuzumab improves the CR rate with acceptable toxicity when administered as consolidation therapy following induction therapy with fludarabine and rituximab.

III. To estimate the progression-free and overall survival of high risk (VH gene unmutated and those with p53 dysfunction) and low-risk (others) patients following therapy with fludarabine and rituximab induction and consolidative alemtuzumab.

IV. To determine the frequency of molecular (PCR) remission following fludarabine and rituximab induction therapy and alemtuzumab consolidation therapy and if this serves as a surrogate marker for prolonged progression-free and overall survival.

SECONDARY OBJECTIVES:

I. To determine the effect of concurrent treatment with fludarabine and rituximab followed by consolidative alemtuzumab on recovery of T-cells, NK cells, and serum immunoglobulin levels.

II. To determine clinical and molecular features that predict for poor response to fludarabine and rituximab induction and subsequent alemtuzumab consolidation therapy.

III. To assess preliminarily the molecular features of CLL at relapse in patients responding to chemoimmunotherapy for CLL.

IV. To determine the frequency of patients who remain at high risk for progression of CLL despite this therapy and who are thus eligible for nonmyeloablative stem cell transplantation studies such as CALGB 109901.

V. To perform limited rituximab pharmacokinetics to determine the ideal schedule of administration for a subsequent rituximab maintenance treatment approach following induction therapy with fludarabine and rituximab.

OUTLINE:

Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.

Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.

Patients are followed at 2 months, every 3 months for 1 year, and then every 6 months for 7 years from study entry.