Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00042796

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of decitabine in treating children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: decitabine	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study Of Decitabine (DAC) (IND # 50733) In Children With Relapsed Or Refractory Acute Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: 5-Aza-2'-deoxycytidine

U.S. FDA Resources

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

Study Start Date:

January 2003

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of decitabine that is associated with consistent evidence of deoxyribonucleic acid (DNA) demethylation in children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia.
Determine the dose-limiting toxicity, pharmacokinetics, and antitumor activity of this drug in these patients.
Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global and specific DNA methylation status (using methylation microarrays) and hemoglobin F levels in these patients.
Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global changes in gene expression profiles using cDNA microarrays and drug sensitivity of blast cells by MTT assays in these patients.
Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, deletions and single nucleotide polymorphisms in genomic DNA of deoxycytidine kinase and cytidine deaminase genes in these patients.
Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, acetylation and methylation of histones H3 and H4 and helicase protein expression in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease type (acute myeloid leukemia vs acute lymphoblastic leukemia).

Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 4-6 weeks for a minimum of 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 15-21 patients will be accrued for this study within 7.5-21 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed acute myeloid leukemia (AML) or acute lymphoblastic leukemia that is considered refractory to conventional therapy or for which no conventional therapy exists
For patients with AML:
- M3 marrow OR
- M2 marrow with at least 15% blasts
- Secondary AML allowed
CNS involvement allowed

PATIENT CHARACTERISTICS:

Age

Under 22

Performance status

Karnofsky 50-100% (age 17 to 21)
Lansky 50-100% (age 16 and under)

Life expectancy

At least 8 weeks

Hematopoietic

See Chemotherapy
WBC no greater than 30,000/mm^3
Patients with granulocytopenia, anemia, and/or thrombocytopenia are eligible but are not evaluable for hematological toxicity

Hepatic

Bilirubin no greater than 1.5 times normal
ALT no greater than 5 times normal
Albumin at least 2 g/dL

Renal

Creatinine no greater than 1.5 times normal OR
Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal

Cardiovascular

Shortening fraction at least 27% by echocardiogram OR
Ejection fraction at least 50% by MUGA scan

Pulmonary

No evidence of dyspnea at rest
No exercise intolerance
Oxygen saturation greater than 94% by pulse oximetry

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Concurrent seizure disorder allowed if well controlled on anticonvulsants
No grade 2 or greater CNS toxicity
No uncontrolled infection (i.e., infections associated with fever, dissemination, hemodynamic instability [requiring pressor support], and progression while on therapy)
No active graft-versus-host disease (GVHD)
- GVHD well controlled on cyclosporine allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy

Recovered from prior immunotherapy
At least 1 week since prior biologic agents
At least 6 months since prior allogeneic bone marrow transplantation (BMT)
At least 3 months since prior autologous BMT
No concurrent sargramostim (GM-CSF)
No concurrent prophylactic filgrastim (G-CSF) during the first course of therapy

Chemotherapy

Recovered from prior chemotherapy
At least 4 weeks since prior cytarabine
At least 24 hours since prior cytoreductive therapy with hydroxyurea (20-30 mg/kg/day for no more than 7 days) to lower the WBC to no greater than 30,000/mm^3
No concurrent intrathecal therapy during the first course of decitabine

Endocrine therapy

Not specified

Radiotherapy

Recovered from prior radiotherapy
At least 2 weeks since prior local palliative radiotherapy (small port)
At least 6 weeks since prior cranial or craniospinal radiotherapy

Surgery

Not specified

Other

No concurrent medications that induce cytidine deaminase or deoxycytidine kinase (e.g., cytarabine)
No concurrent medications that mask poor or deteriorating organ function
No concurrent CNS prophylaxis during the first course of decitabine
Concurrent anticonvulsants with no known interactions with decitabine allowed
Concurrent antibacterial or antifungal therapies for controlled infections allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00042796

Show 21 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Norman J. Lacayo, MD

Stanford University

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000069471, COG-ADVL0114
Study First Received:	August 5, 2002
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00042796 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute promyelocytic leukemia (M3)
secondary acute myeloid leukemia

Additional relevant MeSH terms:

Antimetabolites
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Immunoproliferative Disorders
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Enzyme Inhibitors

Leukemia, Myeloid
Decitabine
Leukemia, Myeloid, Acute
Pharmacologic Actions
Leukemia
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on November 27, 2009