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

September 4, 2015 updated by: Merck Sharp & Dohme LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

71

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: vorinostat
Other Names:
  • SAHA
  • MK-0683
Drug: decitabine
Other Names:
  • Dacogen
Experimental: 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.
Drug: vorinostat
Other Names:
  • SAHA
  • MK-0683
Drug: decitabine
Other Names:
  • Dacogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day 1 to 28 of Cycle 1

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Refractory or Relapse Acute Myelogenous Leukemia (AML)
Time Frame: Approximately 6 months
Objective Response Rate was measured in participants with refractory or relapse AML (acute myelogenous leukemia) in combination with Decitabine who were treated with vorinostat and decitabine on either a concurrent or sequential regimen. The Objective response was defined as any confirmed complete remission or any confirmed partial remission for AML participants and complete remission, confirmed partial remission or confirmed hematologic improvement for Myelodysplastic Syndrome (MDS) participants.
Approximately 6 months
Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Intermediate-high Risk Myelodysplastic Syndrome (MDS) or Untreated Acute Myelogenous Leukemia (AML)
Time Frame: Approximately 6 months
Objective Response Rate was measured in participants with intermediate-high risk MDS or untreated AML who were treated with vorinostat and decitabine either on a concurrent or sequential regimen. The Objective response was defined as any confirmed complete remission or any confirmed partial remission for AML participants and complete remission, confirmed partial remission or confirmed hematologic improvement for MDS participants.
Approximately 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

May 24, 2007

First Submitted That Met QC Criteria

May 25, 2007

First Posted (Estimate)

May 28, 2007

Study Record Updates

Last Update Posted (Estimate)

September 21, 2015

Last Update Submitted That Met QC Criteria

September 4, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0683-055
  • 2007_500

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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