AALL1131, A Phase III Randomized Trial for Newly Diagnosed High Risk B-precursor Acute Lymphoblastic Leukemia (ALL) Testing Clofarabine (IND# 73789, NSC# 606869) in the Very High Risk Stratum

Summary

Eligible participants will be assigned to a risk classification of HR or VHR based on factors that include the result of research tests, as well as age and the presence or absence of leukemia cells in the spinal fluid or brain.
HR ALL participants will receive standard Induction therapy, and then will be randomly assigned to 1 of 2 treatment arms for all phases of post-Induction therapy. The 2 treatment arms are the same except for differences in the type of intrathecal therapy subjects receive. Arm A: Patients receive therapy that is standard including age adjusted intrathecal methotrexate. This is the standard arm. Arm B: Patients receive therapy that is standard with triple intrathecal therapy (methotrexate, hydrocortisone and cytosine arabinoside) instead of intrathecal methotrexate. This is the experimental arm.
VHR ALL participants will receive standard Induction therapy, and then will be randomly assigned to one of three treatment arms for all phases of post-Induction therapy. The same treatment is given on all 3 arms of the study during most phases of therapy: during the first half of Consolidation, during Interim Maintenance I and II, during the first half of Delayed Intensification, as well as during Maintenance. Differences in the therapy subjects receive will be during the second halves of Consolidation and Delayed Intensification therapies.
Control Arm: Participants will receive standard chemotherapy in the following post-Induction stages:
 Consolidation, Interim Maintenance I, Delayed intensification, Interim Maintenance II, Maintenance
Experimental Arm 1: Participants will receive experimental therapy containing cyclophosphamide + etoposide
Experimental Arm 2: Participants will receive experimental therapy containing cyclophosphamide + etoposide + clofarabine

The first 40 subjects to be treated on Experimental Arm 2 will receive clofarabine at 30 mg/m2 once a day and be observed very closely for side effects. The dose will be adjusted for later subjects based on the observed side effects.
DS HR-ALL participants will receive modified therapy that is less intense than standard chemotherapy. All participants will receive the same treatment in the first half of Induction, except for the type of steroid used, which will be determined by age. A bone marrow test will be done during Induction treatment to assess disease response, and the result will used to determine if the drug daunorubicin will be used. During Interim Maintenance, participants will be given intermediate dose of methotrexate instead of high dose methotrexate. During Maintenance, participants will receive the drugs vincristine and prednisone at regular 12 week intervals instead of standard 4 week intervals. Male participants will be treated for the same length of time as female participants, instead of the standard 12 months longer.

Participant Eligibility

 Enrolled on AALL08B1 prior to enrollment on AALL1131
 Participants must be >365 days and <31 years of age
 Meet WBC criteria as outlined in protocol
 Newly diagnosed B-precursor ALL. Patients with Down syndrome are also eligible.
 Females of childbearing potential must have a negative pregnancy test
 Patients of childbearing potential must agree to use an effective birth control method
 Female patients who are lactating must agree to stop breast-feeding
 All patients and/or their parents or legal guardians must sign a written informed consent