A Phase I Clinical Trial of Vorinostat in Combination With Decitabine in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
Overview
- Phase
- Phase 1
- Intervention
- vorinostat
- Conditions
- Leukemia, Myelocytic, Acute Myelodysplastic Syndromes
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 71
- Primary Endpoint
- Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This study is to evaluate the safety and tolerability of vorinostat in combination with decitabine as well as the in vivo molecular and biological effects of vorinostat in patients with refractory or relapsed Acute Myelogenous Leukemia (AML) and intermediate or high risk as defined by International Prognostic Scoring System (IPSS) Myelodysplastic Syndrome (MDS). Participants with Acute Myelogenous Leukemia or Myelodysplastic Syndrome are eligible.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient is at least 18 years old with refractory/relapsed AML
- •If untreated AML, patient is older than 60 years old and not a candidate for standard chemotherapy
- •Patient is at least 4 weeks from prior treatment and has recovered from all prior treatment side effects
- •Patient has no known liver or kidney problems
- •Patient knows of no reason they can not receive transfusions of blood clotting cells (platelets)
- •Patient is able to swallow capsules
- •Patients both male and female are willing to practice birth control during the study
Exclusion Criteria
- •Patient has received prior treatment with valproic acid, decitabine or azacitidine
- •Being is less than 18 years of age or if patient has untreated AML is below 60 years of age
- •Patient is a women who is pregnant or breastfeeding. Patient has an active infection that requires antibiotics
- •Patient has uncontrolled illness including but not limited to the following: heart problems (congestive heart failure, unstable angina pectoris, cardiac arrhythmia), inflammation of the pancreas; a mental or social condition that may interfere with patient following study procedures
- •Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy. Patient has a known history of hepatitis B or C infection
- •Patient currently has another active cancer other than certain types of skin cancer
- •Patient is heterosexual and able to have a child and is unwilling to practice birth control during the study
Arms & Interventions
Cohort 1: Vorinostat (sequential)
Vorinostat 400 mg capsules once daily given 7, 10 or 14 days in 28 day cycles. Up to 24 months of treatment. Decitabine IV 20 mg/m\^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment.
Intervention: vorinostat
Cohort 1: Vorinostat (sequential)
Vorinostat 400 mg capsules once daily given 7, 10 or 14 days in 28 day cycles. Up to 24 months of treatment. Decitabine IV 20 mg/m\^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment.
Intervention: decitabine
Cohort 2: Vorinostat (concurrent)
Vorinostat 400 mg capsules once daily given 7 days, 14 days with 8 day break after first 7 days or 14 days without break, out of 28 day cycles. Decitabine IV 20 mg/m\^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment.
Intervention: vorinostat
Cohort 2: Vorinostat (concurrent)
Vorinostat 400 mg capsules once daily given 7 days, 14 days with 8 day break after first 7 days or 14 days without break, out of 28 day cycles. Decitabine IV 20 mg/m\^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment.
Intervention: decitabine
Outcomes
Primary Outcomes
Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events
Time Frame: Day 1 to 28 of Cycle 1
Participants who received at least one dose of vorinostat in combination with decitabine intravenous (IV) at a dose of 20 mg/m\^2 daily for 5 days along with oral vorinostat 400 mg once daily for 7 to 14 days in a 28-day cycle concurrently or sequentially, were evaluated to determine the maximum tolerable dose (MTD) determined by the number of participants experiencing dose limiting toxicity (DLT) events defined as any Grade 3 or 4 non-hematological toxicity (reported adverse event) and/or myelosuppression lasting \>42 days.