Trial Information

ALinC 17, Classification ©), B-precursor Induction Treatment (I)

OBJECTIVES:

- To provide the clinical and laboratory data necessary for placing each patient with ALL
onto the proper therapeutic trial. (Classification)

- To provide an administrative base to capture classification data for correlative
studies in ALL treatment protocols and series of historical protocols. (Classification)

- To provide appropriate induction regimens for patients who may then enter risk
specific, post-induction therapeutic trials. (Induction therapy)

- To determine the correlation between event-free survival (EFS) and the following
measures of minimal-residual disease (MRD)/early response (ER): 1) the rate of
peripheral blast count disappearance and the absolute blast count on day 8 as
determined morphologically, by flow cytometry, and using molecular techniques; 2)
Marrow morphology on day 8, and; 3) MRD as determined by flow cytometry and molecular
techniques on bone marrow and peripheral blood samples on day 29. (Induction therapy)

OUTLINE: This is a multicenter study.

- Classification study: Bone marrow or peripheral blood samples are collected and may be
analyzed for B- and T-lineage antigen screening; cytochemical stains; cytogenetics
(karyotype); immunophenotype screening for MLL, E2A-PBX1, TEL-AML1; immunophenotype
detection of minimal-residual disease (MRD); FCM ploidy (DNA index); trisomies 4 and 10
(FISH); molecular testing for BCR/ABL, MLL rearrangements, E2A-PBX1, and TEL-AML1;
molecular detection of MRD - Tγ, Tδ, or IgH; acute lymphoblastic leukemia (ALL) cell
bank; special T-ALL reference laboratory studies (role of tumor suppressor genes in
T-ALL and drug sensitivity profiles in T-ALL); special study for mature B-ALL
[t(18;14)(a24;q32)] by FISH; and hematopathology consultation concerning morphology and
cytochemistry. The immunophenotype results are used to assign patients to a treatment
protocol, to assign patients to post-induction (day 28) risk group and treatment for
patients with B-precursor (non-T, non-B) ALL, and to use as reference laboratory MRD
results.

- Induction therapy study: Patients are entered on stratum 3 (three drugs) for NCI
consensus standard-risk disease (age < 10 years and WBC < 50,000/mm³) or stratum 4
(four drugs) induction therapy for NCI consensus high-risk disease (age ≥ 10 years
and/or WBC ≥ 50,000/mm³ or CNS3 disease or testicular disease).

- Stratum 3: Patients receive oral dexamethasone twice daily on days 1-28;
vincristine sulfate IV on days 1, 8, 15, and 22; pegaspargase intramuscularly (IM)
on day 4, 5, or 6; cytarabine intrathecally (IT) on day 1; and methotrexate IT on
day 8 (some patients also receive methotrexate IT on days 15 and 22).

- Stratum 4: Patients receive oral prednisone twice daily on days 1-28; vincristine
sulfate IV on days 1, 8, 15, and 22; IM SC-PEG E. coli asparaginase IM on days 2,
5, 8, 12, 15, and 19; daunorubicin hydrochloride IV over 15-20 minutes on days 8,
15, and 22; and methotrexate IT on days 1 and 8 (some patients also receive
methotrexate IT on days 15 and 22).

Based on day 29 bone marrow results, patients may start consolidation therapy, undergo
retesting in a week, or receive 2 additional weeks of therapy. Additional therapy comprises
oral prednisone thrice daily for 14 days; vincristine sulfate IV and daunorubicin
hydrochloride IV over 15-20 minutes on days 29 and 36; and IM pegaspargase on day 29, 30, or
31. After successful remission induction, patients are assigned to COG-P9904, COG-P9905, or
COG-P9906 based on the classification study.

Patients undergo bone marrow aspiration on day 8 to determine the prognostic significance of
early remission in the context of this therapy.

After completion of study treatment, patients are followed up every 6 months for 4 years and
annually thereafter.