Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 21 and under NCI COG-AAML00P2 NCT00028899, AAML00P2

Objectives

1. 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.
2. Determine the efficacy of this regimen in these patients.
3. Correlate the likelihood of leukemic blast cells to undergo apoptosis in vitro with the efficacy of this regimen in these patients.
4. 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.

Entry 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

Prior/Concurrent Therapy:

Biologic therapy:

• At least 180 days since prior hematopoietic stem cell transplantation

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

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:

• Shortening fraction more than 27% by echocardiogram or normal for institution

  OR

• Ejection fraction more than 50% by MUGA

Other:

• Not pregnant or nursing

Expected Enrollment

A total of 52 patients will be accrued for this study within 1.5 years.

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.

Aplenc R, Alonzo TA, Gerbing RB, et al.: Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group. J Clin Oncol 26 (14): 2390-3295, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Richard Aplenc, MD, MSCE, Protocol chair		Ph: 267-426-7252

Registry Information
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
Trial Start Date		2002-07-29
Registered in ClinicalTrials.gov		NCT00028899
Date Submitted to PDQ		2001-11-12
Information Last Verified		2006-04-12
NCI Grant/Contract Number		CA13539

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