Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Vorinostat in Treating Patients With Acute Myeloid Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	MAYO-MC0483 JHOC-J0557, JHOC-J0550, 6882, NCI-6882, NCT00305773

Objectives

Primary

1. Determine the toxicity and the proportion of complete remissions associated with two different treatment schedules of vorinostat (SAHA) in patients with acute myeloid leukemia.

Secondary

1. Determine the toxic effects of SAHA in this study population.
2. Examine for preliminary evidence of re-expression of silenced genes in leukemic blasts in response to SAHA.

Entry Criteria

Disease Characteristics:

• Diagnosis of acute myeloid leukemia (AML), meeting 1 of the following criteria:
  • Relapsed AML in the following categories:
    • Good-risk cytogenetics [inv(16), t (8;21)] in second relapse or in first relapse following a remission of < 12 months
    • Acute promyelocytic leukemia (M3) in second relapse or greater AND must have relapsed following both tretinoin-anthracycline-based therapy and arsenic trioxide-based therapy
    • All other relapsed patients are eligible
  • Untreated AML in the following categories:
    • At least 65 years of age
    • Myelodysplastic syndromes-AML (AML with trilineage dysplasia)
    • AML with del5Q or monosomy 5, monosomy 7, or complex cytogenetics (≥ 3 cytogenetic abnormalities)
• Refused or ineligible for potentially curative options such as allogeneic stem cell transplantation
• No clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia

Prior/Concurrent Therapy:

• More than 4 weeks since prior radiotherapy
• More than 2 weeks since prior valproic acid
• More than 3 weeks since other prior treatment for AML, including hematopoietic growth factors
  • Hydroxyurea for WBC > 30,000/mm³ allowed
• Recovered from prior therapy
• No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), epoetin alfa, or darbepoetin alfa
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies for this cancer

Patient Characteristics:

• ECOG performance status (PS) 0-2 or Karnofsky PS ≥ 60%
• Life expectancy ≥ 3 months
• Bilirubin normal unless attributed to hemolysis or Gilbert's disease in the opinion of the investigator
• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
• No uncontrolled intercurrent illness, including any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known HIV positivity

Expected Enrollment

A total of 44 patients will be accrued for this study.

Outcomes

Complete remission attainment following study treatment.

Toxicity during study treatment
Evidence of re-expression of epigenetically silenced genes during course 1

Outline

This is a multicenter, randomized study.

Patients are stratified according to disease status (relapsed vs untreated). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral vorinostat (SAHA) once a day on days 1-21.
• Arm II: Patients receive oral SAHA three times a day on days 1-14.

In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 2 years.

Schaefer EW, Loaiza-Bonilla A, Juckett M, et al.: A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica 94 (10): 1375-82, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Steven Gore, MD, Protocol chair		Ph: 410-955-8781 Email: gorest@jhmi.edu

Registry Information
Official Title		A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)
Trial Start Date		2006-01-25
Trial Completion Date		2010-01-12
Registered in ClinicalTrials.gov		NCT00305773
Date Submitted to PDQ		2005-12-27
Information Last Verified		2009-01-13
NCI Grant/Contract Number		CA15083, CM17104

Back to Top