Trial Information

Protocol for Patients With High Risk (Resistant, Refractory, Relapsed or Adverse Cytogenetic) AML

OBJECTIVES:

- Compare standard induction chemotherapy with cytarabine, daunorubicin, and etoposide vs
fludarabine and cytarabine in terms of achievement of remission, reasons for remission
failure, duration of remission, survival, toxicity, and supportive care needs in
patients with high risk acute myeloid leukemia.

- Determine if the use of filgrastim (G-CSF) or tretinoin administered during and
following chemotherapy improves outcome in this patient population.

- Determine the impact of these treatment regimens on quality of life in these patients.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified
according to type of disease (resistant vs refractory vs relapsed vs adverse cytogenetic),
age (under 15 vs 15 to 29, vs 30 to 49 vs 50-59 vs 60-69 vs 70 and over), performance
status, and de novo and secondary leukemia. Patients with relapsed disease are further
stratified according to duration of first remission (less than 6 months vs 6 to 12 months vs
12 months and over), and prior transplantation (yes vs no).

Patients are randomized into one of two treatment arms for induction chemotherapy.

- Arm I: Patients receive induction chemotherapy consisting of cytarabine IV every 12
hours on days 1-10, daunorubicin IV on days 1, 3, and 5 and etoposide IV over 1 hour on
days 1-5. Patients receive a second course of therapy with cytarabine IV every 12 hours
on days 1-8 and daunorubicin and etoposide as in course 1.

- Arm II: Patients receive 2 courses of induction chemotherapy consisting of fludarabine
IV over 30 minutes followed by cytarabine IV over 4 hours on days 1-5.

Patients are further randomized into one of two treatment arms for colony stimulating factor
therapy.

- Arm I: Patients receive filgrastim (G-CSF) subcutaneously or IV daily beginning on day
1 of each course of induction chemotherapy and continuing until blood counts recover,
for up to a maximum of 28 days.

- Arm II: Patients receive no G-CSF during and following induction chemotherapy. Patients
are further randomized into one of two treatment arms for retinoid therapy.

- Arm I: Patients receive oral tretinoin daily beginning on day 1 of induction
chemotherapy and continuing for up to a maximum of 90 days.

- Arm II: Patients receive no retinoid therapy during and following induction
chemotherapy.

Following completion of induction chemotherapy, patients achieving complete remission and
blood count recovery may receive subsequent therapy consisting of consolidation chemotherapy
and/or autologous or allogeneic transplantation.

Quality of life is assessed at 3 months.

PROJECTED ACCRUAL: Approximately 800-1,000 patients will be accrued for this study within
4-5 years.