Phase 2
N=54
Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes
Myelodysplastic Syndromes
Bottom Line
View on ClinicalTrials.gov: NCT00382200 ↗Enrolled (actual)
54
Serious AEs
74.1%
Results posted
May 2024
Primary outcome: Primary: Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0 — 5; 14; 7; 28 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- decitabine (Drug); tretinoin (Drug); DNA methylation analysis (Genetic); cytogenetic analysis (Genetic); microarray analysis (Genetic); flow cytometry (Other); immunohistochemistry staining method (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Primary completion
- Jan 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0 |
5; 14; 7; 28 | — |
| PRIMARY Maximum Tolerated Dose of Tretinoin When Administered With Decitabine as Determined by NCI CTC v2.0 (Phase II) |
65 | — |
| PRIMARY Overall Response Rate |
4; 6; 2; 13; 0; 4 | — |
| PRIMARY Rate of Hematologic Improvement as Measured by Responding Cell Lines (Erythroid, Platelet, and Neutrophil Response) (Phase II) |
— | — |
| SECONDARY Change in Bone Marrow Function as Measured by Frequency of Transfusion, Bleeding, and Infection as Well as Changes in Bone Marrow Morphology and Cytogenetics |
— | — |
| SECONDARY Differentiation as Measured by Morphology and Flow Cytometry and Apoptosis as Measured by Flow Cytometry |
— | — |
| SECONDARY Gene Expression Changes as Measured by Affymetrix Gene Profiling Studies |
— | — |
| SECONDARY Demethylation of Specific Genes as Measured by Gene Promoter Methylation Studies |
— | — |
| SECONDARY Correlation of Clinical Response, With Gene Expression, Demethylation of Specific Genes, and Flow Cytometric Indicators of Differentiation and Apoptosis |
— | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT00382200). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.