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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00028899
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 20, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndromes Drug: asparaginase Drug: cytarabine Drug: gemtuzumab ozogamicin Drug: mitoxantrone hydrochloride Phase 1

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
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
Study Start Date : July 2002
Actual Primary Completion Date : September 2006
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Outcome Measures
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Primary Outcome Measures :
  1. Event Free Survival [ Time Frame: Length of study ]

Secondary Outcome Measures :
  1. Toxicity
    Toxicity will be monitored through study chair notification and end course reports

  2. Remission Rate [ Time Frame: Length of study ]
    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.

  3. Prognostic Factor Analysis
    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


Eligibility Criteria
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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

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

Other:

  • Not pregnant or nursing

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00028899


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

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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00028899    
Other Study ID Numbers: AAML00P2
COG-AAML00P2 ( Other Identifier: Children's Oncology Group )
CDR0000069145 ( Other Identifier: ClinicalTrials.gov )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: February 20, 2014
Last Verified: February 2014
Keywords provided by Children's Oncology Group:
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
previously treated myelodysplastic syndromes
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Asparaginase
 Mitoxantrone
Gemtuzumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors