Phase I Trial of Vorinostat (MK-0683, SAHA) in Combination With Decitabine in Patients With AML or MDS (MK-0683-055 EXT1)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Clinical Trial of Vorinostat in Combination With Decitabine in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Conditions
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Leukemia, Myelocytic, Acute Myelodysplastic Syndromes, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: vorinostat
* Drug: decitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Vorinostat (sequential)<br>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. | Drug: vorinostat<br> <br> * Other names: SAHA;Drug: decitabine<br> <br> * Other names: Dacogen;|
| Experimental: Cohort 2: Vorinostat (concurrent)<br>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. | Drug: vorinostat<br> <br> * Other names: SAHA;Drug: decitabine<br> <br> * Other names: Dacogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events | 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. | Day 1 to 28 of Cycle 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Myelocytic, Acute Myelodysplastic Syndromes