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Phase 2 Study of Azacitidine (Vidaza) vs MGCD0103 vs Combination in Elderly Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

This study has been terminated.
(Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 with be closed.)
Sponsor:
Information provided by:
MethylGene Inc.
ClinicalTrials.gov Identifier:
NCT00666497
First received: April 23, 2008
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

The purpose of the study is to determine how effective azacitidine, MGCD0103, and the combination of azacitidine and MGCD0103 are in treating AML or MDS in people over 60 years of age.


Condition Intervention Phase
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndrome (MDS)
Drug: Azacitidine
Drug: MGCD0103
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open-Label Study of Azacitidine (Vidaza) vs MGCD0103 vs Azacitidine in Combination With MGCD0103 for the Treatment of Elderly Subjects With Newly Diagnosed AML or Intermediate-2 or High-Risk MDS

Resource links provided by NLM:


Further study details as provided by MethylGene Inc.:

Primary Outcome Measures:
  • Overall response rate as assessed using IWG criteria for AML and MDS [ Time Frame: After 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response; Time to progression; Progression-free survival; RBC transfusion independence; Hematologic improvement; Quality of life; Safety profile; and Pharmacokinetics of azacitidine and MGCD0103 [ Time Frame: After 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: June 2008
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Azacitidine
Drug: Azacitidine
75 mg/m2/day for 5 days, subcutaneous (SC) injection, Days 1 - 5 of every 28-day cycle
Other Name: Vidaza
Experimental: B
MGCD0103
Drug: MGCD0103
90 mg, oral (PO) administration, 3 times per week for 12 doses, 28-day cycle
Experimental: C
Azacitidine + MGCD0103
Drug: Azacitidine
75 mg/m2/day for 5 days, subcutaneous (SC) injection, Days 1 - 5 of every 28-day cycle
Other Name: Vidaza
Drug: MGCD0103
90 mg, oral (PO) administration, 3 times per week for 10 doses, 28-day cycle

Detailed Description:

This randomized, 3-arm Phase 2 study will compare the safety and efficacy of single-agent azacitidine (currently 1 of 3 approved treatments for myelodysplastic syndrome [MDS]) to that of single-agent MGCD0103 and to that of combination therapy with MGCD0103 and azacitidine in elderly patients with acute myelogenous leukemia (AML) or intermediate-2 (Int-2) or high-risk MDS, for whom no standard of care exists. The goal of the study is to determine which of the 3 treatment arms are worthy of further investigation in a subsequent Phase 3 study of elderly subjects with AML or Int-2 or high-risk MDS.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to provide written informed consent, and be willing and able to comply with all the study procedures
  • Must be 60 years of age or older
  • Must have a pathologic confirmation of newly diagnosed (de novo or untreated secondary) AML or newly diagnosed Int-2 or high-risk MDS (IPSS classification) according to WHO criteria
  • Must have a Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Must have adequate organ function, including total bilirubin ≤ 1.5 x upper limit of normal (ULN); AST & ALT ≤ 2.5 x ULN; and serum creatinine ≤ 2.0 x ULN.

Exclusion Criteria:

  • Considered fit for intensive chemotherapy and opt to be treated with intensive chemotherapy
  • Prior transplantation or any prior anticancer therapy (standard or investigational, including chemotherapy, treatment with HDAC inhibitors, or combination HDAC and azacitidine) administered to treat AML or MDS.
  • Clinical evidence of central nervous system (CNS) involvement by leukemia
  • A diagnosis of promyelocytic leukemia
  • Previous or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry
  • Active and uncontrolled clinically significant infection
  • Known positive serology for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) or human immunodeficiency virus (HIV)
  • Less than 4 weeks elapsed since any major surgery
  • Any prior or active disease that may interfere with the procedures or evaluations to be conducted in 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: NCT00666497

Locations
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Canada, British Columbia
Diamond Centre, Leukemia/BMT Program of BC
Vancouver, British Columbia, Canada, V5Z 4E3
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
United Kingdom
University Hospital
Birmingham, United Kingdom, B15 2TH
Royal Bournemouth Hospital
Bournemouth, United Kingdom, BH7 7DW
Kings College Hospital
London, United Kingdom, SE5 9RS
St. Bartholomews Hospital
London, United Kingdom, EC1A 7BE
John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
Sponsors and Collaborators
MethylGene Inc.
Investigators
Study Director: Gregory Reid, MSc, MBA MethylGene Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Gregory Reid, Executive Director, Clinical Development, MethylGene Inc.
ClinicalTrials.gov Identifier: NCT00666497     History of Changes
Other Study ID Numbers: 103 PH GL 2007 CL003
Study First Received: April 23, 2008
Last Updated: October 23, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Spain: Ministry of Health
Sweden: Medical Products Agency

Keywords provided by MethylGene Inc.:
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Azacitidine
Vidaza
MGCD0103
Histone deacetylase inhibitor
DNA methyltransferase inhibitor
Epigenetic Therapy

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

ClinicalTrials.gov processed this record on November 20, 2014