Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes

23:37 EDT 17th September 2014 | BioPortfolio

Summary

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.

Description

OBJECTIVES:

Primary

- 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)

Secondary

- 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

Conditions

Myelodysplastic Syndromes

Intervention

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

Location

Memorial Sloan-Kettering Cancer Center
New York
New York
United States
10065

Status

Active, not recruiting

Source

Memorial Sloan-Kettering Cancer Center

Results (where available)

View Results

Links

Clinical Trials [2254 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...

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 ...

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...

DNA Analysis of Tumor Tissue From Patients With Metastatic Kidney Cancer

RATIONALE: DNA analysis of tumor tissue may help doctors predict how well patients will respond to treatment. PURPOSE: This laboratory study is analyzing the DNA in tumor tissue from pati...

PubMed Articles [27874 Associated PubMed Articles listed on BioPortfolio]

A8.20 Bioconpages - comparison of DNA methylation and gene expression in different immune cells.

Site specific methylation of DNA may contribute to the regulation of gene expression. Microarray based analysis of methylation refers to CpG site selected by a biostatistic algorithm without proof for...

Gene Features Selection for Three-Class Disease Classification via Multiple Orthogonal Partial Least Square Discriminant Analysis and S-Plot Using Microarray Data.

DNA microarray analysis is characterized by obtaining a large number of gene variables from a small number of observations. Cluster analysis is widely used to analyze DNA microarray data to make class...

Decitabine of reduced dosage in chinese patients with myelodysplastic syndrome: a retrospective analysis.

Decitabine has been approved for the treatment of all subtypes of myelodysplastic syndrome (MDS). However, the optimal regimen for decitabine treatment is not well established. In this study, an obser...

Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia.

Chromosome banding analysis is the gold standard method for the identification of recurrent cytogenetic abnormalities in acute myeloid leukaemia (AML). It allows stratification of AML patients into su...

The effects of olanzapine on genome-wide DNA methylation in the hippocampus and cerebellum.

The mechanism of action of olanzapine in treating schizophrenia is not clear. This research reports the effects of a therapeutic equivalent treatment of olanzapine on DNA methylation in a rat model in...

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"

Search BioPortfolio:
Loading