Combination Chemotherapy and Alemtuzumab in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

• Complete response rate for MOAD in combination with Campath in adult patients with relapsed or refractory ALL [ Time Frame: After 6 courses of induction treatment, assessed up to 5 years ] [ Designated as safety issue: No ]
  With this two-stage design, the probability of stopping at the end of the first stage is 0.60 if the true response rate is 50%, but is 0.04 if the true response rate is 75%; this design has a power of 92% and a one-sided type I error of 0.09. The response at another dose level of Campath will be described in technical report separately.
  
  
• Disease-free survival [ Time Frame: From the date of documented complete remission to the date of first treatment failure (relapse or death before relapse), assessed up to 5 years ] [ Designated as safety issue: No ]
  
• Overall survival [ Time Frame: From the date of registration to date of death, assessed up to 5 years ] [ Designated as safety issue: No ]
  
• Toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: From baseline to up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  All toxicities will be monitored closely using ECOG's standard AE mechanism. Dose-limiting toxicity (DLT) is defined as a treatment-related toxicity that happens in induction or consolidation and results in prolonged delay of two weeks or longer, including patients who discontinue therapy permanently due to treatment-related toxicity.
  
  
• Association of CD52 expression levels with outcome [ Time Frame: From baseline to up to 5 years ] [ Designated as safety issue: No ]
  Levels of CD52 expression in terms of intensity of fluorescence staining will be compared between patients who achieve CR and patients who do not, using the Wilcoxon rank sum test. Effect size is defined as the difference in means of the two groups divided by the assumed common standard deviation of the two groups. This power calculation is based on the power of the t-test to detect the same effect size and the Pitman efficiency of the Wilcoxon rank sum test to the t-test being at least 0.864.
  
  
• Correlation of the presence of minimal residual disease with overall outcome [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  
• Minimal residual disease (MRD) levels by flow cytometry [ Time Frame: Day 1 of each course of consolidation therapy ] [ Designated as safety issue: No ]
  MRD levels will be retrospectively correlated with clinical response.
  
  

OBJECTIVES:

I. Determine the complete response rate in patients with relapsed or refractory acute lymphoblastic leukemia treated with methotrexate, vincristine, asparaginase, and dexamethasone (MOAB) in combination with alemtuzumab.

II. Determine disease-free and/or overall survival of patients treated with this regimen.

III. Determine the toxic effects of this regimen in these patients. IV. Correlate the density of CD52 molecules on the surface of leukemic lymphoblasts with response in patients treated with this regimen.

V. Correlate the presence of minimal residual disease at the time of maximal response to this regimen with overall outcome in these patients.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY: Patients receive methotrexate IV on day 1; vincristine IV and asparaginase intramuscularly (IM) on day 2; oral dexamethasone on days 1-10; and alemtuzumab subcutaneously on days 1, 4, and 7. Treatment repeats every 10 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR proceed to consolidation therapy.

CONSOLIDATION THERAPY: Patients receive methotrexate IV on day 1 and asparaginase IM on day 2. Treatment repeats every 10 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in CR proceed to cytoreduction therapy.

CYTOREDUCTION THERAPY: Patients receive vincristine IV and methotrexate IV over 6 hours on day 1; leucovorin calcium IV continuously over 24 hours on days 1 and 2 and then orally 4 times a day on day 3; and oral dexamethasone on days 2-6. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in CR proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive oral mercaptopurine on days 1-30; oral methotrexate on days 1, 8, 15, and 22; vincristine IV on day 1; and oral dexamethasone on days 1-5. Treatment repeats every 30 days for 36 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years from the date of registration to this study.