Vorinostat in Treating Patients With Acute Myeloid Leukemia

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

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

Treatments: Drug: vorinostat

Study type: Interventional

Funder types: NIH

Identifiers

NCT00305773

P30CA015083 (U.S. NIH Grant/Contract)

NCI-2012-01470 (Registry Identifier)

MC0483 (Other Identifier)

6882 (Other Identifier)

JHOC-J0550

CDR0000465213

N01CM62205 (U.S. NIH Grant/Contract)

MAYO-MC0483

NCI-6882

JHOC-J0557

Details and patient eligibility

About

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.

Full 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.

Enrollment: 37 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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37 participants in 2 patient groups

Arm I (once daily vorinostat)

Experimental group

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.

Treatment:

Drug: vorinostat

Drug: vorinostat

Arm II (thrice daily vorinostat)

Experimental group

Description:

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.

Treatment:

Drug: vorinostat

Drug: vorinostat