Monoclonal Antibody Plus Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes
RATIONALE: Drugs used in chemotherapy 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. Combining monoclonal antibody therapy with combination chemotherapy may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of combining gemtuzumab ozogamicin with combination chemotherapy in treating children who have relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome.
Drug: gemtuzumab ozogamicin
Drug: mitoxantrone hydrochloride
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Dose Finding Study of the Safety of Gemtuzumab Ozogamicin Combined With Conventional Chemotherapy for Patients With Relapsed or Refractory Acute Myeloid Leukemia|
- Event Free Survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
- Toxicity [ Designated as safety issue: Yes ]Toxicity will be monitored through study chair notification and end course reports
- Remission Rate [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]The remission rate in each arm will be estimated by the proportion of patients who achieved remission among patients who received GMTZ at the MTD level.
- Prognostic Factor Analysis [ Designated as safety issue: No ]The predictive value of the likelihood of leukemia blast cells to undergo apoptosis and drug resistance of leukemia blast cells will be assessed by logistic regression
|Study Start Date:||July 2002|
|Study Completion Date:||March 2012|
|Primary Completion Date:||September 2006 (Final data collection date for primary outcome measure)|
- Determine the safety and maximum tolerated dose of gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes.
- Determine the efficacy of this regimen in these patients.
- Correlate the likelihood of leukemic blast cells to undergo apoptosis in vitro with the efficacy of this regimen in these patients.
- Correlate drug resistance as manifested by dye efflux or multiple drug resistance-1 expression by leukemic blast cells with the efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study of gemtuzumab ozogamicin. Patients are assigned by cohort to 1 of 2 treatment regimens.
- Regimen A: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-4, mitoxantrone IV over 1 hour on days 3-6, and gemtuzumab ozogamicin IV over 2 hours on day 7.
- Regimen B: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, asparaginase intramuscularly on days 2 and 9, and gemtuzumab ozogamicin IV over 2 hours on day 3.
Cohorts of 3-6 patients receive de-escalating doses of gemtuzumab ozogamicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose below that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed monthly for 6 months, every 2 months for 6 months, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 1.5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00028899
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|Study Chair:||Richard Aplenc, MD, MSCE||Children's Hospital of Philadelphia|