Trial Information

A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg®) During Induction Therapy Versus Standard Induction With Daunomycin and Cytosine Arabinoside Followed by Consolidation and Subsequent Randomization to Post-Consolidation Therapy With Gemtuzumab Ozogamicin (Mylotarg®) or No Additional Therapy For Patients Under Age 61 With Previously Untreated De Novo Acute Myeloid Leukemia (AML)

OBJECTIVES:

- Compare disease-free survival of patients with previously untreated de novo acute
myeloid leukemia treated with induction therapy comprising cytarabine and daunorubicin
with vs without gemtuzumab ozogamicin followed by consolidation therapy comprising
high-dose cytarabine and post-consolidation therapy comprising gemtuzumab ozogamicin vs
no additional therapy.

- Compare the complete remission rate in patients treated with these regimens.

- Compare the frequency and severity of the toxic effects of these regimens in these
patients.

Other objectives (if funding allows):

- Determine the prognostic significance of CD33 expression on the response rate in
patients receiving gemtuzumab ozogamicin.

- Determine the prognostic significance of FLT3 mutations in these patients before
treatment with these regimens.

- Determine the prognostic significance of minimal residual disease in remission
specimens from these patients treated with these regimens.

- Determine the prognostic significance of the flow cytometric detection of minimal
residual disease in specimens collected from these patients treated with these
regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified during induction
therapy according to age (< 35 years vs ≥ 35 years) and during post-consolidation therapy
according to preinduction cytogenetic risk group.

- Induction therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive daunorubicin IV on days 1-3, cytarabine IV continuously on
days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 4. Patients receive
filgrastim (G-CSF) or sargramostim (GM-CSF) IV or subcutaneously once daily
beginning on day 15 and continuing until blood counts recover.

- Arm II: Patients receive daunorubicin, cytarabine, and G-CSF or GM-CSF as in arm
I.

Patients in both arms undergo bone marrow aspiration and biopsy on day 14 (and on day 19, if
applicable) and then proceed to reinduction therapy.

- Reinduction therapy: Patients receive daunorubicin IV on days 1-3 and cytarabine IV
continuously on days 1-7. Patients also receive G-CSF or GM-CSF as in induction
therapy.

Patients who achieve A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease
status proceed to consolidation therapy.

- Consolidation therapy: Patients receive high-dose cytarabine IV over 3 hours twice
daily on days 1, 3, and 5. Treatment repeats every 28 days for 3 courses in the absence
of disease progression or unacceptable toxicity.

Patients who maintain A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease
status after consolidation therapy proceed to post-consolidation therapy.

- Post-consolidation therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Treatment
repeats every 28 days for 3 courses in the absence of disease progression or
unacceptable toxicity.

- Arm II: Patients receive no additional therapy. Patients are observed at days 30
and 60 after randomization.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then
annually for 3 years.

PROJECTED ACCRUAL: A total of 684 patients (342 per treatment arm) will be accrued for this
study within 4.5-5 years.