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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Pilot Study of Phenylbutyrate, Dexamethasone and GM-CSF in Refractory or Relapsed t(8;21) Acute Myeloid Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Biological: sargramostim
* Drug: dexamethasone
* Drug: oral sodium phenylbutyrate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: sargramostim|nan|
|Drug: dexamethasone|nan|
|Drug: oral sodium phenylbutyrate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia