Idarubicin and Ara-C in Combination With Gemtuzumab-Ozogamicin (IAGO) for Young Untreated Patients, Without an HLA Identical Sibling, With High Risk MDS or AML Developing After a Preceding Period With MDS During 6 Months Duration: A Phase II Study
- Determine the feasibility of combining gemtuzumab ozogamicin with idarubicin and
cytarabine with or without cyclophosphamide with total body irradiation vs busulfan
followed by allogeneic stem cell transplantation in patients with previously untreated
high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS.
- Determine the toxicity profile of this regimen in these patients.
- Determine the antileukemic/anti-MDS activity of this regimen in these patients.
- Determine the hepatotoxicity of this regimen, in terms of veno-occlusive disease, in
- Determine the severity of pancytopenia and duration of recovery in patients treated
with this regimen.
OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups.
- Group 1 (for patients with no HLA-matched sibling donor): Patients receive
remission-induction chemotherapy comprising idarubicin IV over 5 minutes on days 1, 3,
and 5; cytarabine IV continuously over 24 hours on days 1-10; and gemtuzumab ozogamicin
IV over 2 hours on day 7. Treatment continues for a second course in the absence of
- Group 2 (for patients with an HLA-matched sibling donor): Patients are randomized to 1
of 2 treatment arms.
- Arm I: Patients receive myeloablative consolidation chemotherapy comprising
cyclophosphamide on days -6 and -5 and total body irradiation twice daily on days
-4 to -2.
- Arm II: Patients receive myeloablative consolidation chemotherapy comprising
busulfan on days -8 to -5 and cyclophosphamide on days -4 and -3.
Patients in both arms may alternatively undergo T-cell depletion and/or a reduced-intensity
Approximately 4-8 weeks after completion of consolidation chemotherapy, all patients in
group 2 undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem
cell transplantation. Patients in group 2 then proceed to remission-induction chemotherapy
as in group 1.
Patients achieving complete remission are recommended for consolidation therapy off study.
Patients are followed monthly for 6 months, every 2 months for 6 months, and then every 3
PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study within 10 months.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Rate of complete remission (CR) or complete remission with incomplete recovery of platelets (CRp) as measured by Cheson response criteria after the start of treatment
Theo De Witte, MD, PhD
Universitair Medisch Centrum St. Radboud - Nijmegen
United States: Federal Government