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

NCT00479232 | Completed Phase 1 Results

• 2 other identifiers: 0683-0552007_500
• Study Type: interventional
• Target: 71
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Leukemia, Myelocytic, Acute Myelodysplastic Syndromes; Myelodysplastic Syndromes

Keywords

Leukemia; Myelocytic; Acute Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• 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

Other Outcomes (2)

• Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Refractory or Relapse Acute Myelogenous Leukemia (AML)

  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)

  Approximately 6 months

Study Arms (2)

Cohort 1: Vorinostat (sequential)

EXPERIMENTAL

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; Drug: decitabine

Cohort 2: Vorinostat (concurrent)

EXPERIMENTAL

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; Drug: decitabine

Interventions

vorinostat DRUG

Also known as: MK-0683, SAHA

Cohort 1: Vorinostat (sequential); Cohort 2: Vorinostat (concurrent)

decitabine DRUG

Also known as: Dacogen

Cohort 1: Vorinostat (sequential); Cohort 2: Vorinostat (concurrent)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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 myelodysplastic syndrome. Br J Haematol. 2014 Oct;167(2):185-93. doi: 10.1111/bjh.13016. Epub 2014 Jul 8.

  PMID: 25040094 RESULT

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

Interventions

Vorinostat; Decitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2007
• First Posted: May 28, 2007
• Study Start: June 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: March 1, 2012
• Last Updated: September 21, 2015
• Results First Posted: August 31, 2011

Record last verified: 2015-09