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Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

Primary Purpose

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)

Status
Terminated
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
decitabine
laboratory biomarker analysis
pharmacological study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Princess Margaret Hospital Phase 2 Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (decitabine)

Arm 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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0

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
Proportion of patients with in-vitro retinoid response
Duration of clinical response
Changes in gene expression, gene methylation and bone marrow aspirate sample measurements
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.

Full Information

First Posted
November 12, 2002
Last Updated
September 27, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00049582
Brief Title
Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Terminated
Study Start Date
September 2002 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (decitabine)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
decitabine
Other Intervention Name(s)
5-aza-dCyd, 5AZA, DAC
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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
Title
Proportion of patients with in-vitro retinoid response
Time Frame
Up to 8 years
Title
Duration of clinical response
Time Frame
Up to 8 years
Title
Changes in gene expression, gene methylation and bone marrow aspirate sample measurements
Description
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.
Time Frame
Up to day 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Minden
Organizational Affiliation
Princess Margaret Hospital Phase 2 Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Hospital Phase 2 Consortium
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

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Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

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