Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes

NCT00382200 | Completed Phase 1 Results

• 2 other identifiers: 06-054MSKCC-06054
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myelodysplastic Syndromes

Keywords

de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes

Outcome Measures

Primary Outcomes (4)

• Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0

  Up to 1 year

• Maximum Tolerated Dose of Tretinoin When Administered With Decitabine as Determined by NCI CTC v2.0 (Phase II)

  Up to 1 year

• Overall Response Rate

  Overall Response Rate is defined as Complete Response + Partial Response

  Up to 1 year

• Rate of Hematologic Improvement as Measured by Responding Cell Lines (Erythroid, Platelet, and Neutrophil Response) (Phase II)

  After each cycle

Secondary Outcomes (5)

• Change in Bone Marrow Function as Measured by Frequency of Transfusion, Bleeding, and Infection as Well as Changes in Bone Marrow Morphology and Cytogenetics

  After each cycle

• Differentiation as Measured by Morphology and Flow Cytometry and Apoptosis as Measured by Flow Cytometry

  After each cycle

• Gene Expression Changes as Measured by Affymetrix Gene Profiling Studies

  After each cycle

• Demethylation of Specific Genes as Measured by Gene Promoter Methylation Studies

  After each cycle

• Correlation of Clinical Response, With Gene Expression, Demethylation of Specific Genes, and Flow Cytometric Indicators of Differentiation and Apoptosis

  After each cycle

Study Arms (1)

Decitabine and All-Trans Retonoic Acid (Tretinoin)

EXPERIMENTAL

Decitabine and All-Trans Retonoic Acid (Tretinoin)

Drug: decitabine; Drug: tretinoin; Genetic: DNA methylation analysis; Genetic: cytogenetic analysis; Genetic: microarray analysis; Other: flow cytometry; Other: immunohistochemistry staining method

Interventions

decitabine DRUG

Decitabine and All-Trans Retonoic Acid (Tretinoin)

tretinoin DRUG

Decitabine and All-Trans Retonoic Acid (Tretinoin)

DNA methylation analysis GENETIC

Decitabine and All-Trans Retonoic Acid (Tretinoin)

cytogenetic analysis GENETIC

Decitabine and All-Trans Retonoic Acid (Tretinoin)

microarray analysis GENETIC

Decitabine and All-Trans Retonoic Acid (Tretinoin)

flow cytometry OTHER

Decitabine and All-Trans Retonoic Acid (Tretinoin)

immunohistochemistry staining method OTHER

Decitabine and All-Trans Retonoic Acid (Tretinoin)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed myelodysplastic syndromes (MDS) * International Prognostic scoring system (IPSS) score ≥ 0.5, including the following: * Untreated or treated intermediate-1 risk disease * Intermediate-2 risk disease * High-risk disease * No treatment-related MDS * Ineligible for transplantation * No decitabine-refractory disease defined as disease progression after discontinuation of therapy * If previously treated with decitabine, must have responded to therapy (hematologic improvement or better per International Working Group Response Criteria) PATIENT CHARACTERISTICS: * Karnofsky performance status 60-100% * Bilirubin ≤ 2.5 mg/dL * AST and ALT ≤ 2 times upper limit of normal (ULN) * Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other medical condition that, in the opinion of the treating physician, would preclude patient compliance or put patient at excessive risk of treatment-related toxicity * No other malignancy that would likely require systemic chemotherapy within 4 months after starting study treatment * No allergy to parabens, vitamin A, or retinoids PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior azacytidine allowed * More than 4 weeks since prior cytotoxic chemotherapy or radiotherapy * More than 4 weeks since prior experimental therapy * Concurrent myeloid growth factors allowed only in the setting of febrile neutropenia according to established guidelines for use

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Decitabine; Tretinoin; DNA Methylation; Cytogenetic Analysis; Microarray Analysis; Flow Cytometry; Immunohistochemistry

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Microchip Analytical Procedures; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Histocytochemistry; Histological Techniques; Immunologic Techniques

Results Point of Contact

• Title: Dr. Raajit Rampal, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

rampalr@mskcc.org

646-608-3746

Study Officials

• Raajit Rampal, MD, PhD

  Memorial SloanKettering Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2006
• First Posted: September 28, 2006
• Study Start: July 1, 2006
• Primary Completion: January 5, 2023
• Study Completion: January 5, 2023
• Last Updated: May 20, 2024
• Results First Posted: May 20, 2024

Record last verified: 2023-01

Locations

US (1)