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Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00049582
First received: November 12, 2002
Last updated: September 27, 2013
Last verified: September 2013

November 12, 2002
September 27, 2013
September 2002
June 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00049582 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • Proportion of patients with in-vitro retinoid response [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Duration of clinical response [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Changes in gene expression, gene methylation and bone marrow aspirate sample measurements [ Time Frame: Up to day 5 ] [ Designated as safety issue: No ]
    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.
Not Provided
Not Provided
Not Provided
 
Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia
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)

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Given IV
    Other Names:
    • 5-aza-dCyd
    • 5AZA
    • DAC
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
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.

Interventions:
  • Drug: decitabine
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
36
Not Provided
June 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00049582
NCI-2012-02502, NCI-2012-02502, CDR0000258121, NCI-5591, PHL-004, PHL-004, 5591, N01CM62203
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Mark Minden Princess Margaret Hospital Phase 2 Consortium
National Cancer Institute (NCI)
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP