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)
18 Years
N/A
Both
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
Trial Information
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)
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Outcome Time Frame:
Up to day 28
Safety Issue:
Yes
Principal Investigator
Mark Minden
Investigator Role:
Principal Investigator
Investigator Affiliation:
Princess Margaret Hospital Phase 2 Consortium
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02502
NCT ID:
NCT00049582
Start Date:
September 2002
Completion Date:
Related Keywords:
- 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
- Congenital Abnormalities
- Neoplasms
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|
