Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	PMH-PHL-004 NCI-5591, NCT00049582, 5591

Objectives

1. Determine the maximum tolerated dose of decitabine in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia.
2. Determine the minimum effective dose of this drug that produces demethylation of DNA with tolerable toxicity in these patients.
3. Determine the minimum effective dose of this drug that augments in vitro responses to retinoids.
4. Determine the pharmacokinetics of this drug in these patients.
5. Determine the clinical response rate of patients treated with this drug.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• 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

Chemotherapy

• 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

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy greater than 3,000 cGy to marrow-producing areas
• At least 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• Prior investigational therapy allowed
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• AST and/or ALT no greater than 1.25 times ULN

Renal

• Creatinine less than 1.7 mg/dL

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Princess Margaret Hospital

Mark Minden, MD, PhD, FRCPC, Protocol chair		Ph: 416-946-2015 Email: minden@oci.utoronto.ca

Registry Information
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)
Trial Start Date		2002-09-17
Registered in ClinicalTrials.gov		NCT00049582
Date Submitted to PDQ		2002-09-20
Information Last Verified		2005-09-08
NCI Grant/Contract Number		CM17107

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