Vorinostat and Azacitidine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00392353|
Recruitment Status : Active, not recruiting
First Posted : October 26, 2006
Last Update Posted : July 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Erythroid Leukemia Acute Megakaryoblastic Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Myelodysplastic Syndrome With Excess Blasts Myelodysplastic Syndrome With Ring Sideroblasts Recurrent Adult Acute Myeloid Leukemia Refractory Anemia||Drug: Azacitidine Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Vorinostat||Phase 1 Phase 2|
I. To evaluate the safety and toxicity of vorinostat in combination with azacitidine in patients with myelodysplastic syndromes (MDS) and some select patients with acute myeloid leukemia (AML) (step 1).
II. To identify doses of both vorinostat and azacitidine for safe combination of the 2 agents that can be administered in repetitive cycles over time for use in phase II studies.
III. To determine the response rate of patients treated with the combination of suberoylanilide hydroxamic acid (SAHA) (vorinostat) and azacitidine at the doses established as safe and effective in Step 1 in an expanded cohort of patients with MDS.
IV. To obtain preliminary data on the effects of treatment with the combination of vorinostat and Aza C (azacitidine) in patients with MDS on a series of biologic surrogate markers including: deoxyribonucleic acid (DNA) methylation of specific genes (e.g. p15); histone acetylation; hematopoietic progenitor growth and differentiation; the fate of the MDS clone and changes in gene expression by array profiling.
I. Determine effect of treatment with the combination on time to response, time to leukemic transformation and frequency of transformation to leukemia in patients with MDS during the phase II segment of the study.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive azacitidine subcutaneously (SC) once daily (QD) on days 1-7 and vorinostat orally (PO) 2-3 times daily on days 3-5, 3-9, or 3-16. Treatment repeats every 28 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed monthly for 6 months and then every 2 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||135 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Study of Vorinostat [Suberoylanilide Hydroxamic Acid (SAHA)] in Combination With Azacitidine in Patients With the Myelodysplastic Syndrome (MDS)|
|Actual Study Start Date :||November 22, 2006|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||June 30, 2022|
Experimental: Treatment (azacitidine, vorinostat)
Patients receive azacitidine SC QD on days 1-7 and vorinostat PO 2-3 times daily on days 3-5, 3-9, or 3-16. Treatment repeats every 28 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Incidence of toxicities of vorinostat in combination with azacitidine graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 (Phase I) [ Time Frame: Up to 1 month post-treatment ]Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimates.
- Objective overall response proportion (complete response [CR] + CR with incomplete blood count + partial response) (Phase II) [ Time Frame: Up to day 168 ]Ninety-five percent confidence intervals will be estimated for the response proportion in all three treatment groups via binomial proportions.
- Distribution of toxicities in the 12th treatment arm (Phase II) [ Time Frame: Up to 1 month post-treatment ]The frequency of subjects experiencing toxicities will be tabulated. Toxicities will be assessed and graded according to CTCAE v. 5.0 terminology. Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimates.
- Time to response [ Time Frame: Up to day 84 ]
- Time to leukemic transformation [ Time Frame: Up to day 84 ]
- Frequency of leukemic transformation [ Time Frame: Up to day 84 ]
- Progression-free survival [ Time Frame: Time from first treatment day until objective or symptomatic progression, assessed up to 8 years ]Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
- Overall survival [ Time Frame: Time from first treatment day until death, assessed up to 8 years ]Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00392353
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|University of Maryland/Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|United States, New York|
|Montefiore Medical Center-Weiler Hospital|
|Bronx, New York, United States, 10461|
|Montefiore Medical Center - Moses Campus|
|Bronx, New York, United States, 10467|
|North Shore University Hospital|
|Manhasset, New York, United States, 11030|
|Mount Sinai Hospital|
|New York, New York, United States, 10029|
|NYP/Weill Cornell Medical Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Lewis R Silverman||Montefiore Medical Center - Moses Campus|