Myelodysplastic SyndromesPhase 1/2NCT00382200
Decitabine and Tretinoin in Treating Patients With Myelodysplastic Syndromes
A Phase 1/2 study testing decitabine, tretinoin and DNA methylation analysis in people with Myelodysplastic Syndromes, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- decitabine, tretinoin and DNA methylation analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to 5 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase I/II Study of Decitabine and All-Trans Retinoic Acid (Tretinoin) for Patients With Myelodysplastic Syndromes
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.
Read the 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.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- decitabine, tretinoin, DNA methylation analysis, cytogenetic analysis, microarray analysis
- Keywords
- de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
decitabineDrug
tretinoinDrug
DNA methylation analysisGenetic
cytogenetic analysisGenetic
microarray analysisGenetic
flow cytometryOther
| Study group | Role | What they receive |
|---|---|---|
| Decitabine and All-Trans Retonoic Acid (Tretinoin) | Experimental | Decitabine and All-Trans Retonoic Acid (Tretinoin) Receives: Drug: decitabine; Drug: tretinoin; Genetic: DNA methylation analysis; Genetic: cytogenetic analysis; Genetic: microarray analysis; Other: flow cytometry; Other: immunohistochemistry staining method |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0
Measured: Up to 1 year
Maximum Tolerated Dose of Tretinoin When Administered With Decitabine as Determined by NCI CTC v2.0 (Phase II)
Measured: Up to 1 year
Overall Response Rate
Overall Response Rate is defined as Complete Response + Partial Response
Measured: Up to 1 year
Rate of Hematologic Improvement as Measured by Responding Cell Lines (Erythroid, Platelet, and Neutrophil Response) (Phase II)
Measured: 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
Measured: After each cycle
Differentiation as Measured by Morphology and Flow Cytometry and Apoptosis as Measured by Flow Cytometry
Measured: After each cycle
Gene Expression Changes as Measured by Affymetrix Gene Profiling Studies
Measured: After each cycle
Demethylation of Specific Genes as Measured by Gene Promoter Methylation Studies
Measured: After each cycle
Correlation of Clinical Response, With Gene Expression, Demethylation of Specific Genes, and Flow Cytometric Indicators of Differentiation and Apoptosis
Measured: After each cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2006 (estimated)
- Study startJul 2006
- Primary completion5 Jan 2023
- Study completion5 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Raajit Rampal, MD, PhD, Study chair, Memorial SloanKettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00382200
- Sponsor's protocol ID
- 06-054
- Other IDs
- MSKCC-06054
- Status last verified
- Jan 2023
- First submitted
- 26 Sep 2006
- Last updated
- 20 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Decitabine and All-Trans Retinoic Acid (Tretinoin) for Patients With Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT00382200
- Acronym / sponsor ID
- 06-054
- Conditions
- Myelodysplastic Syndromes
- Keywords
- de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2006
- Primary completion
- 5 Jan 2023 (actual)
- Study completion
- 5 Jan 2023 (actual)
- First posted
- 28 Sep 2006 (estimated)
- Results
- Posted 20 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine and All-Trans Retonoic Acid (Tretinoin) | Experimental | Drug: decitabine, Drug: tretinoin, Genetic: DNA methylation analysis, Genetic: cytogenetic analysis, Genetic: microarray analysis, Other: flow cytometry, Other: immunohistochemistry staining methodDecitabine and All-Trans Retonoic Acid (Tretinoin) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) |
Primary outcome
Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0
Time frame: Up to 1 year
Maximum Tolerated Dose of Tretinoin When Administered With Decitabine as Determined by NCI CTC v2.0 (Phase II)
Time frame: Up to 1 year
Overall Response Rate
Time frame: Up to 1 year
Overall Response Rate is defined as Complete Response + Partial Response
Rate of Hematologic Improvement as Measured by Responding Cell Lines (Erythroid, Platelet, and Neutrophil Response) (Phase II)
Time frame: After each cycle
5 secondary outcomes
Change in Bone Marrow Function as Measured by Frequency of Transfusion, Bleeding, and Infection as Well as Changes in Bone Marrow Morphology and Cytogenetics
Time frame: After each cycle
Differentiation as Measured by Morphology and Flow Cytometry and Apoptosis as Measured by Flow Cytometry
Time frame: After each cycle
Gene Expression Changes as Measured by Affymetrix Gene Profiling Studies
Time frame: After each cycle
Demethylation of Specific Genes as Measured by Gene Promoter Methylation Studies
Time frame: After each cycle
Correlation of Clinical Response, With Gene Expression, Demethylation of Specific Genes, and Flow Cytometric Indicators of Differentiation and Apoptosis
Time frame: After each cycle
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raajit Rampal, MD, PhD study chair
Memorial SloanKettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing decitabine, tretinoin and DNA methylation analysis in people with Myelodysplastic Syndromes, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0 (time frame: Up to 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2024.