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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00028899

Purpose

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
Leukemia Myelodysplastic Syndromes	Drug: asparaginase Drug: cytarabine Drug: gemtuzumab ozogamicin Drug: mitoxantrone hydrochloride	Phase I

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:

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Cytarabine hydrochloride Mitoxantrone Mitoxantrone hydrochloride Gemtuzumab ozogamicin Cytarabine L-Asparaginase

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	July 2002
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00028899

Show 76 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Richard Aplenc, MD, MSCE

Children's Hospital of Philadelphia

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Aplenc R, Alonzo TA, Gerbing RB, Lange BJ, Hurwitz CA, Wells RJ, Bernstein I, Buckley P, Krimmel K, Smith FO, Sievers EL, Arceci RJ; Children's Oncology Group. 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. 2008 May 10;26(14):2390-3295.

ClinicalTrials.gov Identifier:	NCT00028899 History of Changes
Other Study ID Numbers:	CDR0000069145, COG-AAML00P2
Study First Received:	January 4, 2002
Last Updated:	December 31, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Gemtuzumab
Asparaginase
Cytarabine
Mitoxantrone
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 09, 2012