A Phase I Trial of SAHA (NSC 701852) and Decitabine (IND 50733, NSC 127716) in Patients With Relapsed, Refractory or Poor Prognosis Leukemia
I. To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLT) of
vorinostat in combination with Decitabine in patients with relapsed/refractory or poor
prognosis acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL),
myelodysplastic syndrome (MDS) or chronic myeloid leukemia in accelerated or blastic phase
1.2 To describe the clinical activity of the combination of Decitabine and vorinostat in
this patient population.
1.3 To determine the in vivo molecular effects of this combination. This will include
measuring the effects on DNA methylation, histone H3 and H4 acetylation and changes in gene
1.4 To determine the pharmacokinetic characteristics of the combination.
OUTLINE: This is a dose-escalation study.
Patients receive decitabine IV over 1 hour on days 1-5 and oral vorinostat (SAHA) three
times daily on days 6-19. Courses repeat every 28 days in the absence of disease progression
or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of decitabine and SAHA until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional
patients are treated at that dose.
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose and dose-limiting toxicity of vorinostat and decitabine
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M D Anderson Cancer Center||Houston, Texas 77030|