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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)

Phase 2
Terminated
Conditions
Myelodysplastic Syndrome (MDS)
Acute Myeloid Leukemia (AML)
Interventions
Registration Number
NCT00666497
Lead Sponsor
Mirati Therapeutics Inc.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CAzacitidineAzacitidine + MGCD0103
BMGCD0103MGCD0103
CMGCD0103Azacitidine + MGCD0103
AAzacitidineAzacitidine
Primary Outcome Measures
NameTimeMethod
Overall response rate as assessed using IWG criteria for AML and MDSAfter 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment
Secondary Outcome Measures
NameTimeMethod
Duration of response; Time to progression; Progression-free survival; RBC transfusion independence; Hematologic improvement; Quality of life; Safety profile; and Pharmacokinetics of azacitidine and MGCD0103After 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment

Trial Locations

Locations (8)

St. Bartholomews Hospital

🇬🇧

London, United Kingdom

Diamond Centre, Leukemia/BMT Program of BC

🇨🇦

Vancouver, British Columbia, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

Royal Bournemouth Hospital

🇬🇧

Bournemouth, United Kingdom

University Hospital

🇬🇧

Birmingham, United Kingdom

Kings College Hospital

🇬🇧

London, United Kingdom

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

John Radcliffe Hospital

🇬🇧

Oxford, United Kingdom

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