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


Phase 2
18 Years
N/A
Not Enrolling
Both
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

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Confirmed Complete Response (CR) Rate

Outcome Description:

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.

Outcome Time Frame:

Up to 2 years

Safety Issue:

No

Principal Investigator

Steven Gore

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01470

NCT ID:

NCT00305773

Start Date:

January 2006

Completion Date:

Related Keywords:

  • 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
  • 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

Name

Location

Mayo ClinicRochester, Minnesota  55905