Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)
A Phase 2 Trial of Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS) Who Are Ineligible for Other Leukemia Protocols
2 other identifiers
interventional
110
1 country
1
Brief Summary
The goal of this clinical research study is to learn if the combination of azacitidine and vorinostat can help to control AML or MDS better than azacitidine alone. The safety of this drug combination will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 leukemia
Started Sep 2009
Typical duration for phase_2 leukemia
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 28, 2009
CompletedFirst Posted
Study publicly available on registry
July 29, 2009
CompletedStudy Start
First participant enrolled
September 8, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedResults Posted
Study results publicly available
July 2, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
August 3, 2017
CompletedFebruary 24, 2020
February 1, 2020
5.6 years
July 28, 2009
May 29, 2015
February 10, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Survival at Day 60
Assessment of survival for outcome done on 60 days following therapy and includes participants alive for at least 60 days. Survival is calculated from start of therapy until death from any cause.
Phase I, Baseline to 60 days following first treatment.
Response Rate
Number of participants with Complete Response (CR) in AML requiring disappearance of all signs and symptoms related to disease, normalization of peripheral counts (absolute neutrophil count 10\^9/L or more, platelet count 100 x 10\^9/L or more), and a marrow with 5% or less marrow blasts; a hematologic improvement (HI) defined as a CR except for a platelet count increase by 50% to above 30 x 10\^9/L. For MDS, the International Working Group criteria used to assess response.
12-18 Months
Survival at Day 60
Assessment of survival for outcome done on 60 days following therapy and includes participants alive for at least 60 days. Survival is calculated from start of therapy until death from any cause.
Phase II, Baseline to 60 days following first treatment.
Study Arms (2)
Vorinostat with Azacitidine
EXPERIMENTALARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Azacitidine
EXPERIMENTALARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Interventions
200 mg by mouth three (3) times per day with food for 5 days (Days 1 - 5)
75 mg/m\^2/day given intravenously over 15 - 30 minutes daily for 5 days (Days 1 - 5)
Eligibility Criteria
You may qualify if:
- Patients with newly diagnosed AML or MDS (Intermediate 1 or higher risk)
- Patient must have at least one of the following: a. Creatinine \>/= 2 mg/dL; b. total Bilirubin \>/= 2 mg/dL; c.ECOG Performance Status equal to 3 or 4; and d. is ineligible for participation on a protocol of higher priority
- Patients must provide written informed consent.
- Patients must be age \> 18 years due to lack of safety information with these agents in children.
- Patient agrees to: 1) Use 2 adequate methods of contraception to prevent pregnancy (either 2 barrier methods or a barrier method plus a hormonal contraceptive method) or 2) abstain from heterosexual activity throughout the study starting with Visit 1.
- Female patients of childbearing potential should have a negative pregnancy test (serum) within 72 hrs. of study enrollment.
You may not qualify if:
- Patients must not have the favorable cytogenetic abnormalities of inv (16), t (16;16), t (8;21), or t (15;17).
- Patients receiving any anti-leukemic therapy with the exception of Hydroxyurea prior to study enrollment. Prior growth factor therapy is acceptable. Hydroxyurea could be used at the discretion of the treating physician. A single or a two day dose of cytarabine (up to 3 g/m\^2) for emergency use is allowed as prior therapy.
- Patient has a prior history of treatment with HDAC inhibitors. Patients who have received valproic acid (VPA) for the treatment of seizures may be enrolled on this study, but must not have received VPA within 30 days of study enrollment.
- Patient is unable to take and/or tolerate oral medications on a continuous basis, examples include patients on a ventilator, or have altered mental status that precludes safe oral route of administration.
- Patient has active hepatitis A, B, or C infection.
- Patient is pregnant or breast-feeding.
- Patient has a known allergy or hypersensitivity to any component of vorinostat or azacitidine.
- History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Merck Sharp & Dohme LLCcollaborator
- Celgene Corporationcollaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Montalban-Bravo G, Huang X, Naqvi K, Jabbour E, Borthakur G, DiNardo CD, Pemmaraju N, Cortes J, Verstovsek S, Kadia T, Daver N, Wierda W, Alvarado Y, Konopleva M, Ravandi F, Estrov Z, Jain N, Alfonso A, Brandt M, Sneed T, Chen HC, Yang H, Bueso-Ramos C, Pierce S, Estey E, Bohannan Z, Kantarjian HM, Garcia-Manero G. A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials. Leukemia. 2017 Feb;31(2):318-324. doi: 10.1038/leu.2016.303. Epub 2016 Oct 31.
PMID: 27795561DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Guillermo Garcia-Manero, MD/Professor, Leukemia Department
- Organization
- University of Texas (UT) MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Guillermo Garcia-Manero, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 28, 2009
First Posted
July 29, 2009
Study Start
September 8, 2009
Primary Completion
April 1, 2015
Study Completion
August 3, 2017
Last Updated
February 24, 2020
Results First Posted
July 2, 2015
Record last verified: 2020-02