The purpose of the study is to determine if temozolomide plus vorinostat in combination can control relapsed or refractory acute myeloid leukemia (AML) and determine if this combination can be safely taken. The study will look at the side effects of the temozolomide plus vorinostat in combination and whether the treatment schedule is tolerated.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01550224.
PRIMARY OBJECTIVES:
I. To determine the clinical efficacy of 2 different treatment regimens, stratified by the O-6-methylguanine-DNA methyltransferase gene (MGMT) methylation status, of temozolomide plus vorinostat in patients with AML >= age 18 and with relapsed/refractory AML.
SECONDARY OBJECTIVES:
I. To determine the toxicity profile of these treatment regimens in this patient population.
II. To determine whether vorinostat, when given prior to and concurrent with temozolomide, can sensitize leukemic blasts with methylated or non-methylated MGMT promoter to conventional doses of temozolomide.
III. To determine, as reported with descriptive statistics, the survival, overall and disease-free, for patients receiving combination therapy.
IV. To determine the responses rates in each cohort of patients individually (methylated and non methylated).
OUTLINE: Patients with methylated MGMT promoter are assigned to group 1, and patients with non-methylated MGMT promoter are assigned to group 2.
GROUP 1:
Induction Therapy: Patients receive vorinostat orally (PO) thrice daily (TID) on days 1-3 and receive vorinostat PO and temozolomide PO once daily (QD) on days 4-11. Patients not achieving complete remission after 1 course may receive a second course.
Consolidation Therapy: Patients receive vorinostat PO and temozolomide PO QD on days 1-5. Treatment repeats every 4-5 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
GROUP 2:
Induction Therapy: Patients receive temozolomide PO QD on days 1-14 and vorinostat PO TID days 18-24. Patients not achieving complete remission after 1 course may receive a second course.
Consolidation Therapy: Patients receive temozolomide PO QD on days 1-14 and receive temozolomide PO and vorinostat PO QD on days 15-19. Treatment repeats every 6-7 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 weeks for 6 months.
Lead OrganizationStanford Cancer Institute Palo Alto
Principal InvestigatorBruno Carneiro de Medeiros
