Clinical trial NCT00666497: Phase 2 Study of Azacitidine (Vidaza) vs MGCD0103 vs Combination in Elderly Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Myelodysplastic Syndrome (MDS)
Keywords: Acute Myeloid Leukemia
Myelodysplastic Syndrome
Azacitidine
Vidaza
MGCD0103
Histone deacetylase inhibitor
DNA methyltransferase inhibitor
Epigenetic Therapy
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2008-04-25
Enrollment: 6
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall response rate as assessed using IWG criteria for AML and MDS
timeFrame: After 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment
Secondary outcomes:
measure: 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
timeFrame: After 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Vancouver
country: Canada
facility: Diamond Centre, Leukemia/BMT Program of BC
state: British Columbia
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Birmingham
country: United Kingdom
facility: University Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: London
country: United Kingdom
facility: St. Bartholomews Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: MethylGene Inc.
name: Gregory Reid, MSc, MBA
role: STUDY_DIRECTOR
References: