Vorinostat in Treating Patients With Acute Myeloid Leukemia

NCT ID: NCT00305773

Last Updated: 2014-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2010-01-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given orally once daily

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.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given orally three times daily

Interventions

vorinostat

Given orally once daily

Intervention Type: DRUG

vorinostat

Given orally three times daily

Intervention Type: DRUG

Other Intervention Names

L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Gore

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

Schaefer EW, Loaiza-Bonilla A, Juckett M, DiPersio JF, Roy V, Slack J, Wu W, Laumann K, Espinoza-Delgado I, Gore SD; Mayo P2C Phase II Consortium. A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica. 2009 Oct;94(10):1375-82. doi: 10.3324/haematol.2009.009217.

Reference Type: DERIVED

PMID: 19794082 (View on PubMed)

Other Identifiers

NCI-2012-01470

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000465213

Identifier Type: -

Identifier Source: secondary_id

JHOC-J0557

Identifier Type: -

Identifier Source: secondary_id

MAYO-MC0483

Identifier Type: -

Identifier Source: secondary_id

JHOC-J0550

Identifier Type: -

Identifier Source: secondary_id

NCI-6882

Identifier Type: -

Identifier Source: secondary_id

MC0483

Identifier Type: OTHER

Identifier Source: secondary_id

6882

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62205

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01470

Identifier Type: -

Identifier Source: org_study_id