Trial Information

Medical Research Council Working Party on Leukaemia in Childhood Acute Myeloid Leukaemia Trial 12

OBJECTIVES:

- Compare two induction schedules with respect to achievement and duration of remission,
survival, toxicity, and supportive care requirements in children with previously
untreated acute myeloid leukemia.

- Compare 4 versus 5 courses of treatment in total (where the final course is either
chemotherapy or bone marrow transplantation) with respect to remission duration,
relapse rates, deaths in remission, and overall survival in these patients.

- Compare the value of allogeneic bone marrow transplantation versus conventional
chemotherapy with respect to remission duration, relapse rates, deaths in remission,
and overall survival in these patients.

- Reduce toxicity without compromising survival by restricting the number of patients
receiving bone marrow transplant in this study.

OUTLINE: This is a randomized study. Patients are first randomized to one of two induction
treatment arms.

- Induction Arm I: Patients receive 2 courses of cytarabine IV push every 12 hours on
days 1-10 or 1-8 (20 or 16 doses); daunorubicin IV over 6 hours on days 1, 3, and 5;
and etoposide IV over 4 hours on days 1-5 (5 doses).

- Induction Arm II: Patients receive 2 courses of mitoxantrone IV over 6 hours on days 1,
3, and 5; cytarabine IV push every 12 hours on days 1-10 or 1-8 (20 or 16 doses); and
etoposide IV over 4 hours on days 1-5 (5 doses).

Patients with no CNS disease at diagnosis receive 3 courses of triple intrathecal therapy
(methotrexate, cytarabine, and hydrocortisone), one after each of the first 3 courses of
chemotherapy. Patients with CNS disease receive at least 6 courses of intrathecal therapy (2
courses per week), then monthly courses until the final course of chemotherapy is complete.

Patients in complete response after induction course 2 continue on this study. Patients not
in complete response after induction course 2 are taken off study and are eligible for the
current Medical Research Council (MRC) refractory/relapse study or another therapy.

Course 3: All patients continuing on this study receive amsacrine IV over 1 hour daily on
days 1-5, cytarabine continuous IV infusion daily on days 1-5, and etoposide IV over 4 hours
on days 1-5 as course 3. After course 3, patients are assigned to two risk groups: good risk
patients, and standard and poor risk patients.

Standard and poor risk patients with no matched sibling donor and good risk patients are
then further randomized to consolidation in arms I or II.

- Arm I: Patients receive mitoxantrone IV over 6 hours on days 1-5 and cytarabine IV over
2 hours every 12 hours on days 1-3 (4 courses of chemotherapy total).

- Arm II: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and
9, and asparaginase subcutaneous infusion 3 hours after completion of the last
cytarabine doses on days 2 and 9, followed by a course of mitoxantrone and cytarabine
as in arm I (5 courses of chemotherapy total).

Standard and poor risk children with matched sibling donor are randomized to arms III or IV.

- Arm III: Patients receive no consolidation treatment (3 courses of chemotherapy total)
plus bone marrow transplantation.

- Arm IV: Patients receive cytarabine and asparaginase as in arm II (4 courses of
chemotherapy total) plus bone marrow transplantation.

Patients are followed for at least 1 year.

PROJECTED ACCRUAL: Approximately 2,000 patients will be accrued into this study over 5
years.