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

National Heart, Lung, and Blood Institute (NHLBI)

Overview

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.

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Conditions

Leukemia

Interventions

sargramostimBIOLOGICAL

dexamethasoneDRUG

oral sodium phenylbutyrateDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

National Heart, Lung, and Blood Institute

Bethesda, Maryland, United States

Mount Sinai Medical Center, NY

New York, New York, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Data from ClinicalTrials.gov

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