Idarubicin, Cytarabine, and Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome
RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as gemtuzumab ozogamicin, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells. Giving healthy stem cells from a donor whose blood closely resembles the patient's blood will help the patient's bone marrow make new stem cells that become red blood cells, white blood cells, and platelets.
PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with gemtuzumab ozogamicin works in treating patients with previously untreated high-risk myelodysplastic syndrome or acute myeloid leukemia secondary to myelodysplastic syndrome.
Drug: gemtuzumab ozogamicin
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- 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 [ Designated as safety issue: No ]
- Severe toxicity after the start of treatment [ Designated as safety issue: Yes ]
- Disease-free survival from CR/CRp [ Designated as safety issue: No ]
- Duration of overall survival [ Designated as safety issue: No ]
- Severity of pancytopenia and duration of recovery in patients who reached CR/CRp after the start of treatment [ Designated as safety issue: No ]
|Study Start Date:||November 2003|
|Primary Completion Date:||November 2006 (Final data collection date for primary outcome measure)|
- 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 these patients.
- 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 unacceptable toxicity.
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 conditioning regimen.
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 months thereafter.
PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study within 10 months.
|Brugge, Belgium, 8000|
|Cliniques Universitaires Saint-Luc|
|Brussels, Belgium, 1200|
|Institut Jules Bordet|
|Brussels, Belgium, 1000|
|H. Hartziekenhuis - Roeselaere.|
|Roeselare, Belgium, 8800|
|Ruprecht - Karls - Universitaet Heidelberg|
|Heidelberg, Germany, D-69117|
|Onze Lieve Vrouwe Gasthuis|
|Amsterdam, Netherlands, 1091 HA|
|Leiden University Medical Center|
|Leiden, Netherlands, 2300 CA|
|Universitair Medisch Centrum St. Radboud - Nijmegen|
|Nijmegen, Netherlands, NL-6500 HB|
|Basel, Switzerland, CH-4031|
|Study Chair:||Theo De Witte, MD, PhD||Universitair Medisch Centrum St. Radboud - Nijmegen|