Phenylbutyrate, Dexamethasone, and Sargramostim in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia

National Institutes of Health (NIH)

Status and phase: Completed; Phase 2

Conditions: Leukemia

Treatments: Drug: dexamethasone; Drug: oral sodium phenylbutyrate; Biological: sargramostim

Study type: Interventional

Funder types: NIH

Identifiers

NCT00006240

NCI-171

CDR0000068165

NHLBI-00-H-0156

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of combining phenylbutyrate, dexamethasone, and sargramostim in treating patients who have refractory or relapsed acute myeloid leukemia.

Full description

OBJECTIVES:

• Determine the objective response (complete hematologic remission induction) of phenylbutyrate, dexamethasone, and sargramostim (GM-CSF) in patients with refractory or relapsed t(8;21) acute myeloid leukemia.
• Determine the correlation between histone acetylation, differentiation, and apoptosis in bone marrow mononuclear cells with response rate in patients treated with this regimen.
• Determine the overall survival of patients on this regimen.
• Determine the correlation between histone acetylation, differentiation, and apoptosis in bone marrow mononuclear cells with pharmacokinetics of this regimen in these patients.
• Determine the safety and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive phenylbutyrate IV continuously and sargramostim (GM-CSF) subcutaneously on days 1-7 and 15-21. Patients also receive oral dexamethasone on days 1-4 and 15-18. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity until complete hematologic remission is induced. Patients with stable disease at the end of 1 course receive at least 2 additional courses.

Patients are followed twice a week for 3 months, monthly for 1 year, every three months for the next 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for this study in at least 2 years.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of t(8;21) acute myeloid leukemia (AML)

  • Failed standard induction chemotherapy or stem cell transplantation (SCT) OR
  • Relapsed after standard induction chemotherapy or SCT OR
  • Refused or not a candidate for SCT or matched allogeneic sibling bone marrow transplantation or donor lymphocyte infusion OR
  • Refused of not a candidate for autologous SCT or bone marrow transplantation

• No CNS leukemia

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 7 days

Hematopoietic:

• Not specified

Hepatic:

• AST or ALT no greater than 3 times upper limit of normal (ULN)
• Bilirubin no greater than 3 times ULN
• No hepatic disease that would preclude study

Renal:

• Creatinine no greater than 2 mg/dL
• Creatinine clearance at least 60 mL/min
• No renal disease that would preclude study

Cardiovascular:

• No cardiac disease that would preclude study
• No New York Heart Association class III or IV heart disease
• No myocardial infarction within past 8 weeks

Other:

• No active infection except cystitis
• Not pregnant or nursing
• No altered mental status or seizure disorder
• No other serious disease that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 3 weeks since prior investigational antineoplastic drugs