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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00479232
First received: May 24, 2007
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Leukemia, Myelocytic, Acute Myelodysplastic Syndromes
Myelodysplastic Syndromes
Drug: vorinostat
Drug: decitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial of Vorinostat in Combination With Decitabine in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events [ Time Frame: Day 1 to 28 of Cycle 1 ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Refractory or Relapse Acute Myelogenous Leukemia (AML) [ Time Frame: Approximately 6 months ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 71
Study Start Date: June 2007
Study Completion Date: March 2012
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • MK-0683
  • SAHA
Drug: decitabine
Other Name: 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:
  • MK-0683
  • SAHA
Drug: decitabine
Other Name: Dacogen

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00479232

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00479232     History of Changes
Other Study ID Numbers: 0683-055, 2007_500
Study First Received: May 24, 2007
Results First Received: April 28, 2011
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Leukemia
Myelocytic
Acute Myelodysplastic Syndromes

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Decitabine
Vorinostat
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014