Ignite Creation Date:
2025-12-26 @ 12:14 PM
Ignite Modification Date:
2025-12-26 @ 12:14 PM
Study NCT ID:
NCT00382200
Status:
COMPLETED
Last Update Posted:
2024-05-20
First Post:
2006-09-26
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes
Sponsor:
Memorial Sloan Kettering Cancer Center
Organization:
Study Overview
Official Title:
Phase I/II Study of Decitabine and All-Trans Retinoic Acid (Tretinoin) for Patients With Myelodysplastic Syndromes
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Detailed 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.
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 Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| MSKCC-06054 | None | None | View |