Monoclonal Antibody Plus Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

Children's Oncology Group

Status and phase

Completed

Phase 1

Conditions

Leukemia

Myelodysplastic Syndromes

Treatments

Drug: gemtuzumab ozogamicin

Drug: cytarabine

Drug: asparaginase

Drug: mitoxantrone hydrochloride

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00028899

COG-AAML00P2 (Other Identifier)

AAML00P2

CDR0000069145 (Other Identifier)

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

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.

Enrollment

47 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Diagnosis of primary acute myeloid leukemia (AML) or myelodysplastic syndromes
- Relapsed (remission duration less than 1 year) OR
- Failed induction (failed to achieve an initial complete response)
Patients with AML as a second malignant neoplasm allowed provided no other prior therapy for AML
M2 or M3 bone marrow aspirate at time of study entry
No Fanconi's anemia
No known CNS leukemia

PATIENT CHARACTERISTICS:

Age:

21 and under

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 1.5 times normal
AST or ALT less than 2.5 times upper limit of normal
No history of veno-occlusive disease of the liver defined as weight increase of more than 5% over baseline and serum bilirubin greater than 5 mg/dL within 20 days after receipt of chemotherapy

Renal:

Creatinine no greater than 1.5 times normal OR
Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70 mL/min OR
Equivalent GFR by institutional normal range

Cardiovascular: