Trial Information

A Phase II Study of Double Induction Chemotherapy for Newly Diagnosed Non-L3 Adult Acute Lymphoblastic Leukemia With Investigation of Minimal Residual Disease and Risk of Relapse Following Maintenance Chemotherapy

OBJECTIVES:

Primary

- Determine the probability of 1-year continuous complete remission in patients with
newly diagnosed acute lymphoblastic leukemia treated with first induction chemotherapy
comprising daunorubicin, vincristine, prednisone, and pegaspargase; and second
induction chemotherapy comprising high-dose cytarabine and mitoxantrone.

Secondary

- Determine the frequency and severity of toxic effects of these induction regimens
followed by consolidation therapy comprising cyclophosphamide, cytarabine,
mercaptopurine, and methotrexate and maintenance chemotherapy comprising
mercaptopurine, methotrexate, vincristine, doxorubicin, dexamethasone,
cyclophosphamide, thioguanine, and cytarabine in these patients.

Other objectives (if funding allows):

- To evaluate in a preliminary manner the significance of detecting minimal residual
disease as a prognostic factor for survival and relapse-free survival of patients
receiving chemotherapy

- To evaluate in a preliminary manner the pattern of gene expression of patients entered
onto the trial and its relationship to cytogenetics/FISH risk classification, overall
survival, and relapse-free survival

OUTLINE: This is a multicenter study.

- First induction chemotherapy: Patients receive daunorubicin IV on days 1-3; vincristine
IV on days 1, 8, 15, and 22; prednisone IV or orally on days 1-28, followed by a taper
to day 35; and pegaspargase IV or subcutaneously (SC) on day 15. Patients with CNS
leukemia also receive methotrexate intrathecally (IT) or intraventricularly twice
weekly and oral leucovorin calcium four times daily for 4 doses after each
administration of methotrexate. When blasts are no longer present in the spinal fluid,
patients receive methotrexate IT or intraventricularly once weekly for 4 weeks and then
once monthly for 1 year.

Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1
peripheral blood status or those with resistant disease proceed to second induction therapy.

- Second induction chemotherapy: Patients receive high-dose cytarabine IV on days 1-5;
mitoxantrone IV on day 3; and filgrastim (G-CSF) SC or IV beginning on day 7 and
continuing until blood counts recover. Patients with CNS leukemia also receive
methotrexate and leucovorin calcium as in first induction chemotherapy.

Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1
peripheral blood status with no extramedullary disease (other than CNS involvement) proceed
to consolidation chemotherapy. Patients with resistant disease OR Philadelphia chromosome-
or BCR/ABL-positive disease are removed from the study after receiving double induction
chemotherapy.

- Consolidation chemotherapy: Patients receive cyclophosphamide IV on days 1, 15, and 29;
cytarabine IV on days 2-5 and 16-19; oral mercaptopurine on days 1-28; and methotrexate
IT or intraventricularly on days 2, 9, 16, and 23. Patients with CNS leukemia also
undergo cranial radiotherapy once daily, 5 days a week, for 2 weeks.

Patients in complete remission proceed to maintenance chemotherapy.

- Maintenance chemotherapy:

- Course 1: Patients receive oral mercaptopurine on days 1-63 and oral methotrexate
on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients proceed to course 2 after
blood counts recover.

- Course 2: Patients receive vincristine IV and doxorubicin IV on days 1, 8, 15, and
22 and oral dexamethasone on days 1-28. Patients proceed to course 3 after blood
counts recover.

- Course 3: Patients receive cyclophosphamide IV on day 1; oral thioguanine on days
1-14; and cytarabine IV on days 3-6 and 10-13. Patients proceed to course 4 after
blood counts recover.

- Course 4: Patients receive oral mercaptopurine once daily for 2 years and oral
methotrexate once weekly for 2 years.

Treatment continues in the absence of disease relapse or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 1 year, every 6
months for 1 year, and then annually for 3 years.