Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 1

Conditions: Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Previously Treated Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Secondary Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Secondary Acute Myeloid Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Recurrent Adult Acute Myeloid Leukemia

Treatments: Drug: decitabine; Other: laboratory biomarker analysis; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00049582

NCI-5591

5591 (Other Identifier)

NCI-2012-02502 (Registry Identifier)

N01CM62203 (U.S. NIH Grant/Contract)

CDR0000258121

PHL-004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Treatment (decitabine)

Experimental group

Description:

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.

Treatment:

Other: pharmacological study

Other: laboratory biomarker analysis

Drug: decitabine