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Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00948064
First received: July 28, 2009
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: Vorinostat
Drug: Azacitidine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Response Rate [ Time Frame: 12-18 Months ] [ Designated as safety issue: No ]
    Percentage of participants with responses of Complete response (CR) in AML requiring disappearance of all signs and symptoms related to disease, normalization of peripheral counts (absolute neutrophil count 109/L or more, platelet count 100 x 109/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 109/L. For MDS, the International Working Group criteria used to assess response.


Estimated Enrollment: 80
Study Start Date: August 2009
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat with Azacitidine
ARM 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.
Drug: Vorinostat
200 mg by mouth three (3) times per day with food for 5 days (Days 1 - 5)
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
Drug: Azacitidine
75 mg/m^2/day given intravenously over 15 - 30 minutes daily for 5 days (Days 1 - 5)
Other Names:
  • 5-Azacitidine
  • 5-Aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
Experimental: Azacitidine
ARM 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.
Drug: Azacitidine
75 mg/m^2/day given intravenously over 15 - 30 minutes daily for 5 days (Days 1 - 5)
Other Names:
  • 5-Azacitidine
  • 5-Aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with newly diagnosed AML or MDS (Intermediate 1 or higher risk)
  2. 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
  3. Patients must provide written informed consent.
  4. Patients must be age > 18 years due to lack of safety information with these agents in children.
  5. 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.
  6. Female patients of childbearing potential should have a negative pregnancy test (serum) within 72 hrs. of study enrollment.

Exclusion Criteria:

  1. Patients must not have the favorable cytogenetic abnormalities of inv (16), t (16;16), t (8;21), or t (15;17).
  2. 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.
  3. 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.
  4. 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.
  5. Patient has active hepatitis A, B, or C infection.
  6. Patient is pregnant or breast-feeding.
  7. Patient has a known allergy or hypersensitivity to any component of vorinostat or azacitidine.
  8. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948064

Locations
United States, Texas
UT MD Anderson Cancer
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Celgene Corporation
Investigators
Principal Investigator: Guillermo Garcia-Manero, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00948064     History of Changes
Other Study ID Numbers: 2007-0685, NCI-2009-01495
Study First Received: July 28, 2009
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute Myelogenous Leukemia
AML
Myelodysplastic Syndrome
MDS
Vorinostat
SAHA
Suberoylanilide Hydroxamic Acid
MSK-390
Zolinza
Azacitidine
5-Azacitidine
5-Aza
Vidaza
5-AZC
AZA-CR
Ladakamycin
NSC-102816

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Azacitidine
Vorinostat
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014