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Vorinostat in Treating Patients With Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00305773
First received: March 21, 2006
Last updated: March 28, 2013
Last verified: March 2013
History of Changes
  Purpose

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


Condition Intervention Phase
Adult Acute Erythroid Leukemia (M6)
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Acute Promyelocytic Leukemia (M3)
Recurrent Adult Acute Myeloid Leukemia
Refractory Cytopenia With Multilineage Dysplasia
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
 Drug: vorinostat
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)

Resource links provided by NLM:

Drug Information available for: Vorinostat
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Confirmed Complete Response (CR) Rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

    The confirmed complete response rate was estimated by the number of participants with CR divided by the total number of evaluable participants.

    According to the International Working Group (IWG) Criteria for response in AML, to be considered a CR, the following must be met for at least 4 weeks: ANC > 1500/mL, platelets > 100000/mL, no circulating blasts, bone marrow cellularity >20% (biopsy), trilineage maturation, < 5% bone marrow blasts, no auer rods and no extramedullary disease.



Secondary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: Duration of study (up to 2 years) ] [ Designated as safety issue: Yes ]
    Time to Progression (TTP) for each patient will be calculated as the number of days from date of registration to either date when disease progression was documented or date of last evaluation without disease progression. The TTP distribution will be estimated using the method of Kaplan-Meier

  • Overall Survival (OS) [ Time Frame: Duration of study (up to 2 years) ] [ Designated as safety issue: No ]
    Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.

  • Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events [ Time Frame: Up to 30 days of the participant's last treatment ] [ Designated as safety issue: Yes ]

    Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.

    Description of Grades:

    Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death



Other Outcome Measures:
  • Time to Treatment Failure (TTF) [ Time Frame: Duration of treatment (up to 17 cycles) ] [ Designated as safety issue: No ]
    Time to treatment failure (TTF) was defined as the time from registration to until the date of treatment discontinuation of any reason. Patients receiving treatment at the time of analysis were considered censored. The median TTF with 95% CI was estimated using the Kaplan Meier method.


Enrollment: 44
Study Start Date: January 2006
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (once daily vorinostat)
Patients receive oral vorinostat (SAHA) once a day on days 1-21. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
 Drug: vorinostat
Given orally once daily
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Experimental: Arm B (thrice daily vorinostat)
Patients receive oral SAHA three times a day on days 1-14. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
 Drug: vorinostat
Given orally three times daily
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza

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 A: 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 B: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00305773

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Steven Gore Mayo Clinic
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00305773     History of Changes
Other Study ID Numbers: NCI-2012-01470, MC0483, N01CM62205, CDR0000465213
Study First Received: March 21, 2006
Results First Received: March 28, 2013
Last Updated: March 28, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Leukemia, Promyelocytic, Acute
Leukemia, Myelomonocytic, Chronic
Neoplasms by Histologic Type
Neoplasms
 Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Vorinostat
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013