Vorinostat in Treating Patients With Acute Myeloid Leukemia

Brief Title

Vorinostat in Treating Patients With Acute Myeloid Leukemia

Official Title

A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)

Brief Summary

      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. 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.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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 OBJECTIVES:

      I. Determine the toxic effects of SAHA in this study population. II. 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. In both arms,
      treatment repeats every 21 days for up to 17 courses in the absence of disease progression or
      unacceptable toxicity.

      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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Confirmed Complete Response (CR) Rate

Secondary Outcome

 Time to Progression (TTP)

Condition

Adult Acute Erythroid Leukemia (M6)

Intervention

vorinostat

Study Arms / Comparison Groups

 Arm I (once daily vorinostat)

Description:  Patients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

37

Start Date

January 2006

Completion Date

January 2010

Primary Completion Date

May 2009

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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

          -  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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Steven Gore, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00305773

Organization ID

NCI-2012-01470

Secondary IDs

NCI-2012-01470

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Steven Gore, Principal Investigator, Mayo Clinic

Verification Date

December 2012