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

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00006240

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: sargramostim Drug: dexamethasone Drug: oral sodium phenylbutyrate	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2000

Actual Study Completion Date :

Aug 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
2	National Heart, Lung, and Blood Institute	Bethesda	Maryland	United States	20892
3	Mount Sinai Medical Center, NY	New York	New York	United States	10029
4	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213-3489