Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes

2014-07-23 16:35:14 | BioPortfolio


RATIONALE: Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of myelodysplastic cells, either by killing the cells or by stopping them from dividing. Tretinoin and decitabine may help myelodysplastic cells become more like normal cells, and to grow and spread more slowly. Giving decitabine together with tretinoin may be an effective treatment for myelodysplastic syndromes.

PURPOSE: This phase I/II trial is studying the side effects and best dose of tretinoin when given together with decitabine in treating patients with myelodysplastic syndromes.




- Determine the hematologic and nonhematologic toxicities of decitabine in combination with tretinoin in patients with myelodysplastic syndromes. (Phase I)

- Determine the maximum tolerated dose of tretinoin when administered with decitabine in these patients. (Phase I)

- Determine the clinical remission rate (complete and partial remission) in patients treated with this regimen. (Phase II)

- Determine the rate of hematologic improvement in these patients. (Phase II)


- Determine the efficacy of this regimen, in terms of improved bone marrow function, by monitoring frequency of transfusion, bleeding, and infection, as well as changes in bone marrow morphology and cytogenetics in these patients.

- Assess differentiation by morphology and flow cytometry and apoptosis by flow cytometry in patients treated with this regimen.

- Determine if gene expression changes in these patients are induced by this regimen.

- Determine the efficacy of this regimen, in terms of inducing demethylation of specific genes, in these patients.

- Correlate clinical response with gene expression, demethylation of specific genes, and flow cytometric indicators of differentiation and apoptosis.

OUTLINE: This is a phase I, dose-escalation study of tretinoin followed by a phase II, open-label study.

- Phase I: Patients receive decitabine IV over 1 hour once daily on days 1-5 followed by oral tretinoin twice daily on days 10-19. Treatment repeats every 28 days for a minimum of 4 courses in the absence of disease progression or excessive toxicity. Patients who achieve a partial or complete response after completing 6 courses of treatment may receive 4 additional courses up to a total of 10 courses. Patients with stable disease or hematologic improvement are removed from study.

Cohorts of 3-6 patients receive escalating doses of tretinoin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity attributable to tretinoin at any dose level during course 1. A total of 6 patients are treated at the MTD.

- Phase II: Patients receive decitabine as in phase I and tretinoin at the MTD. Patients undergo blood and bone marrow collection periodically during study for correlative demethylation and gene profiling studies and for evidence of differentiation and apoptosis. Samples are examined by flow cytometry, cytogenetics, histochemistry, and array-based whole genome methylation analysis.

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Myelodysplastic Syndromes


decitabine, tretinoin, DNA methylation analysis, cytogenetic analysis, microarray analysis, flow cytometry, immunohistochemistry staining method


Memorial Sloan-Kettering Cancer Center
New York
New York
United States


Active, not recruiting


Memorial Sloan-Kettering Cancer Center

Results (where available)

View Results


Published on BioPortfolio: 2014-07-23T16:35:14-0400

Clinical Trials [3148 Associated Clinical Trials listed on BioPortfolio]

Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

This phase II trial is studying how well decitabine works in treating patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as decitabine, work in dif...

Biomarker Changes in Samples From Young Patients With Acute Myeloid Leukemia

RATIONALE: Studying samples of blood or tumor tissue from patients with cancer in the laboratory may help doctors learn about changes that occur in DNA and identify biomarkers related to c...

Research Study in Patients With Advanced Epithelial Ovarian Cancer

RATIONALE: Analyzing tissue samples from patients in the laboratory may help doctors learn more about cancer. PURPOSE: The purpose of this study is to analyze tissue samples from patients...

Biomarkers in Patients at Risk of Developing Myelodysplastic Syndrome or Other Disorders and in Healthy Participants

RATIONALE: Studying samples of blood and bone marrow in the laboratory from patients at risk of developing myelodysplastic syndrome may help doctors learn more about changes that occur in ...

DNA Analysis of Tumor Tissue From Patients With Acute Myeloid Leukemia

RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It ...

PubMed Articles [28436 Associated PubMed Articles listed on BioPortfolio]

A Parallel and Sensitive Software Tool for Methylation Analysis on Multicore Platforms.

DNA methylation analysis suffers from very long processing time, since the advent of Next-Generation Sequencers (NGS) has shifted the bottleneck of genomic studies from the sequencers that obtain the ...

Single-Nucleotide Polymorphism-Microarray Ploidy Analysis of Paraffin-Embedded Products of Conception in Recurrent Pregnancy Loss Evaluations.

To compare the analysis of chromosome number from paraffin-embedded products of conception using single-nucleotide polymorphism (SNP) microarray with the recommended screening for the evaluation of co...

Comparative analysis of methods to determine DNA methylation levels of a tumor-related miRNA gene.

Quantifying levels of DNA methylation in tumors is a useful approach for the identification of potential tumor suppressors and to find biomarkers that can be used as prognostic or therapeutic indicato...

Correlation between promoter methylation in the GSTP1 gene and hepatocellular carcinoma development: a meta-analysis.

Epigenetic silencing of the GSTP1 gene by promoter methylation has been associated with increased risk and shortened survival in patients with hepatocellular carcinoma (HCC). We therefore conducted a ...

RSPH9 methylation pattern as a prognostic indicator in patients with non-muscle invasive bladder cancer.

DNA methylation is a frequent and early epigenetic event with potential application as a biomarker for cancer detection and an indicator of disease evolution. The aim of the present study was to ident...

Medical and Biotech [MESH] Definitions

The simultaneous analysis, on a microchip, of multiple samples or targets arranged in an array format.

MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Included are such techniques as IN SITU HYBRIDIZATION of chromosomes for CYTOGENETIC ANALYSIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS of gene expression patterns in disease states; identification of pathogenic organisms by analysis of species specific DNA sequences; and detection of mutations with POLYMERASE CHAIN REACTION.

A method of chemical analysis based on the detection of characteristic radionuclides following a nuclear bombardment. It is also known as radioactivity analysis. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

Analysis based on the mathematical function first formulated by Jean-Baptiste-Joseph Fourier in 1807. The function, known as the Fourier transform, describes the sinusoidal pattern of any fluctuating pattern in the physical world in terms of its amplitude and its phase. It has broad applications in biomedicine, e.g., analysis of the x-ray crystallography data pivotal in identifying the double helical nature of DNA and in analysis of other molecules, including viruses, and the modified back-projection algorithm universally used in computerized tomography imaging, etc. (From Segen, The Dictionary of Modern Medicine, 1992)

A multistage process that includes DNA cloning, physical mapping, subcloning, sequencing, and information analysis.

More From BioPortfolio on "Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes"


Relevant Topics

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...

Searches Linking to this Trial