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

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00479232
• Other study ID #: 0683-055
• Secondary ID: 2007_500
• Status: Completed
• Phase: Phase 1
• First received: May 24, 2007
• Last updated: September 4, 2015
• Start date: June 2007
• Est. completion date: March 2012

Study information

• Verified date: September 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: March 2012
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Myelocytic, Acute Myelodysplastic Syndromes
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• vorinostat

• decitabine

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Kirschbaum M, Gojo I, Goldberg SL, Bredeson C, Kujawski LA, Yang A, Marks P, Frankel P, Sun X, Tosolini A, Eid JE, Lubiniecki GM, Issa JP. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or my — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Refractory or Relapse Acute Myelogenous Leukemia (AML)	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	No
Other	Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Intermediate-high Risk Myelodysplastic Syndrome (MDS) or Untreated Acute Myelogenous Leukemia (AML)	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	No
Primary	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	Yes