phenylbutyrate, dexamethasone, and sargramostim in treating patients with refractory or relapsed acute myeloid leukemia

Conditions: Leukemia

Summary: 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.

Eligibility 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

Keywords: recurrent adult acute myeloid leukemia