A Phase I, Dose-Finding Trial of Sodium Phenylbutrate (NSC 657802) in Combination With All Trans-retinoic Acid (ATRA, NSC 122758) in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)
- Determine the safety and toxicity of phenylbutyrate and tretinoin in patients with
myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.
- Determine the pharmacokinetic interaction of this regimen in these patients.
- Determine any potential therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose escalation study of tretinoin.
Patients receive phenylbutyrate IV continuously on days 1-7 of weeks 1, 5, 7, 9, 11, 13, 15,
17, and 19. Patients also receive oral tretinoin three times daily on days 1-7 of weeks 3,
5, 7, 9, 11, 13, 15, 17, and 19. Treatment continues in the absence of disease progression
or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tretinoin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6
patients experience dose limiting toxicities.
An additional cohort of 6 patients is accrued at the MTD. These patients receive
phenylbutyrate IV continuously on days 1-3 of weeks 1 and 3-18. These patients also receive
oral tretinoin three times daily on days 1-3 of weeks 2-18. Treatment continues in the
absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 18 months.
Primary Purpose: Treatment
Steven D. Gore, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|