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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006240
• Other study ID #: CDR0000068165
• Secondary ID: NHLBI-00-H-0156N
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2000
• Last updated: April 27, 2015
• Start date: October 2000
• Est. completion date: August 2001

Study information

• Verified date: November 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: August 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• sargramostim

Drug:
• dexamethasone

• oral sodium phenylbutyrate

Locations

Country	Name	City	State
United States	National Heart, Lung, and Blood Institute	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Mount Sinai Medical Center, NY	New York	New York
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States,