Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP
- Compare the feasibility, toxicity, and antileukemic activity of two different dosing
regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients
with previously untreated acute myeloid leukemia who are not candidates for intensive
chemotherapy. (phase II)
- Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase
II vs standard supportive care, in terms of overall survival, in these patients. (phase
OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase
III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over),
CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC
before hydroxyurea administration (< 30,000/mm^3 vs ≥ 30,000/mm^3), WHO performance status
(0-1 vs 2 vs 3-4), and participating center.
- Phase II: Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and
8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours
every 4 weeks for up to 8 courses in the absence of disease progression or
- Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with
stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks
for up to 8 courses in the absence of disease progression or unacceptable
- Arm III: Patients receive standard supportive care.
- Phase III: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive the selected treatment (arm I or arm II) from phase II.
- Arm II: Patients receive standard supportive care. Patients who receive GO
treatment are followed monthly for 1 year and then every 3 months thereafter.
Patients who receive standard supportive care are followed at least every 4 weeks.
PROJECTED ACCRUAL: A total of 259 patients (75 for phase II [25 per treatment arm] and 184
for phase III [92 per treatment arm]) will be accrued for this study within 2.5 years.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients able to start continuation therapy (Phase II)
Sergio Amadori, MD
EORTC - AZIENDA OSPEDALLERA UNIVERSITARIA - POLICLINICO TOR VERGATA, IT
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)