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Vorinostat in Treating Patients With Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT00305773
Recruitment Status : Completed
First Posted : March 22, 2006
Results First Posted : May 16, 2013
Last Update Posted : May 19, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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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.

Condition or disease Intervention/treatment 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

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)
Study Start Date : January 2006
Actual Primary Completion Date : May 2009
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Vorinostat

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm I (once daily vorinostat)
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.
 Drug: vorinostat
Given orally once daily
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Experimental: Arm II (thrice daily vorinostat)
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.
 Drug: vorinostat
Given orally three times daily
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza


Outcome Measures
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Primary Outcome Measures :
  1. Confirmed Complete Response (CR) Rate [ Time Frame: Up to 2 years ]

    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 :
  1. Time to Progression (TTP) [ Time Frame: Duration of study (up to 2 years) ]
    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

  2. Overall Survival (OS) [ Time Frame: Duration of study (up to 2 years) ]
    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.

  3. Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events [ Time Frame: Duration of study (up to 2 years) ]

    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:
  1. Time to Treatment Failure (TTF) [ Time Frame: Duration of treatment (up to 17 cycles) ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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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
NCI-2012-01470 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000465213
JHOC-J0557
MAYO-MC0483
JHOC-J0550
NCI-6882
MC0483 ( Other Identifier: Mayo Clinic )
6882 ( Other Identifier: CTEP )
N01CM62205 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: March 22, 2006    Key Record Dates
Results First Posted: May 16, 2013
Last Update Posted: May 19, 2014
Last Verified: December 2012

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