Vorinostat in Treating Patients With Acute Myeloid Leukemia

Condition(s) targeted: Leukemia; Myelodysplastic Syndromes

Intervention: vorinostat (Drug); enzyme inhibitor therapy (Procedure)

Phase: Phase 2

Status: Suspended

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
Steven D. Gore, MD, Study Chair, Affiliation: Sidney Kimmel Comprehensive Cancer Center

RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for their growth. Giving the drug in different ways may kill more cancer cells. PURPOSE: This randomized phase II trial is studying two different schedules of vorinostat to see how well they work in treating patients with acute myeloid leukemia.

Official title: A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)

Study design: Treatment, Randomized

Primary outcome: Complete remission attainment following study treatment.

Secondary outcome:

Toxicity during study treatment

Evidence of re-expression of epigenetically silenced genes during course 1

Detailed description: OBJECTIVES: Primary 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 Determine the toxic effects of SAHA in this study population. Examine for preliminary evidence of re-expression of silenced genes in leukemic blasts in response to SAHA. 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. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 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 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/mm^3 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

Mayo Clinic Scottsdale, Scottsdale, Arizona 85259-5499, United States

Mayo Clinic - Jacksonville, Jacksonville, Florida 32224, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis, Missouri 63110, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: January 2006
Last updated: December 25, 2007