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Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

This study has been terminated.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00049582
First Posted: January 27, 2003
Last Update Posted: September 30, 2013
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.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This phase I trial is studying the side effects and best dose of decitabine in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

Condition Intervention Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative de Novo Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Adult Acute Myeloid Leukemia Drug: decitabine Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of 5-Aza-2'-Deoxycytidine (Decitabine) as a Biologic Modifier of Retinoid Responsive Genes in Patients With High-Risk Myelodysplastic Syndromes and Acute Myelogenous Leukemia (De-novo, Relapsed or Secondary)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to day 28 ]

Secondary Outcome Measures:
  • Minimal effective dose of decitabine that will lead to demethylation of deoxyribonucleic acid (DNA) with tolerable toxicity as assessed by RXR gene [ Time Frame: Up to day 28 ]
  • Proportion of patients with in-vitro retinoid response [ Time Frame: Up to 8 years ]
  • Duration of clinical response [ Time Frame: Up to 8 years ]
  • Changes in gene expression, gene methylation and bone marrow aspirate sample measurements [ Time Frame: Up to day 5 ]
    The effect on gene expression due to pharmacological exposures (ie retinoic acid receptor [RAR] or retinoid X receptor [RXR]) will be assessed using chi-square tests.


Enrollment: 36
Study Start Date: September 2002
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (decitabine)

Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of decitabine in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia.

II. Determine the minimum effective dose of this drug that produces demethylation of DNA with tolerable toxicity in these patients.

III. Determine the minimum effective dose of this drug that augments in vitro responses to retinoids.

IV. Determine the pharmacokinetics of this drug in these patients. V. Determine the clinical response rate of patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days 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 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 18 months.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • One of the following diagnoses:

    • High-risk myelodysplastic syndromes (MDS)
    • Acute myeloid leukemia (AML)

      • De novo, secondary, or relapsed disease
      • Any number of prior regimens for primary or relapsed disease
  • Ineligible for or refuses aggressive management
  • Measurable disease, defined as:

    • More than 5% blasts in bone marrow of patients with MDS
    • More than 30% blasts in bone marrow of patients with AML
  • Involvement of cerebrospinal fluid allowed
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • See Disease Characteristics
  • Bilirubin no greater than 1.25 times upper limit of normal (ULN)
  • AST and/or ALT no greater than 1.25 times ULN
  • Creatinine less than 1.7 mg/dL
  • Creatinine clearance at least 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No ongoing or active infection
  • No other uncontrolled illness that would preclude study participation
  • No psychiatric illness or social situation that would preclude study compliance
  • No prior allergic reactions to compounds of similar chemical or biological composition to decitabine
  • No other active malignancy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • At least 4 weeks since prior biologic therapy (e.g., interferon, filgrastim [G-CSF], sargramostim [GM-CSF], thrombopoietin, or epoetin alfa)
  • No concurrent hematopoietic growth factors (GM-CSF, thrombopoietin, or epoetin alfa)
  • No concurrent prophylactic G-CSF
  • Prior intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement
  • At least 4 weeks since prior chemotherapy (except low-dose chemotherapy administered to maintain WBC counts) (6 weeks for nitrosoureas or mitomycin) and recovered
  • At least 24 hours since prior hydroxyurea
  • Concurrent intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement
  • No prior radiotherapy greater than 3,000 cGy to marrow-producing areas
  • At least 4 weeks since prior radiotherapy and recovered
  • Prior investigational therapy allowed
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapy
  Contacts and Locations
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): NCT00049582


Locations
Canada, Ontario
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark Minden Princess Margaret Hospital Phase 2 Consortium
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00049582     History of Changes
Other Study ID Numbers: NCI-2012-02502
NCI-2012-02502 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000258121
NCI-5591
PHL-004
PHL-004 ( Other Identifier: Princess Margaret Hospital Phase 2 Consortium )
5591 ( Other Identifier: CTEP )
N01CM62203 ( U.S. NIH Grant/Contract )
First Submitted: November 12, 2002
First Posted: January 27, 2003
Last Update Posted: September 30, 2013
Last Verified: September 2013

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasm Metastasis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplastic Processes
Decitabine
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors