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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group Identifier:
First received: January 4, 2002
Last updated: February 18, 2014
Last verified: February 2014

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.

Condition Intervention Phase
Myelodysplastic Syndromes
Drug: asparaginase
Drug: cytarabine
Drug: gemtuzumab ozogamicin
Drug: mitoxantrone hydrochloride
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event Free Survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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

Enrollment: 47
Study Start Date: July 2002
Study Completion Date: March 2012
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Detailed Description:


  • 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.


Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • 21 and under

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • Not specified


  • 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


  • 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


  • Shortening fraction more than 27% by echocardiogram or normal for institution OR
  • Ejection fraction more than 50% by MUGA


  • Not pregnant or nursing


Biologic therapy:

  • At least 180 days since prior hematopoietic stem cell transplantation


  • Not specified

Endocrine therapy:

  • Not specified


  • Not specified


  • Not specified
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Please refer to this study by its identifier: NCT00028899

  Show 76 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Richard Aplenc, MD, MSCE Children's Hospital of Philadelphia
  More Information

Additional Information:
Responsible Party: Children's Oncology Group Identifier: NCT00028899     History of Changes
Other Study ID Numbers: AAML00P2, COG-AAML00P2, CDR0000069145
Study First Received: January 4, 2002
Last Updated: February 18, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Precancerous Conditions
Antineoplastic Agents
Central Nervous System Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors processed this record on November 25, 2015