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

Acute Myeloid Leukemia (AML) Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00666497
• Other study ID #: 103 PH GL 2007 CL003
• Status: Terminated
• Phase: Phase 2
• First received: April 23, 2008
• Last updated: April 22, 2015
• Start date: June 2008
• Est. completion date: April 2009

Study information

• Verified date: April 2015
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: Ministry of HealthSpain: Ministry of HealthSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Azacitidine
75 mg/m2/day for 5 days, subcutaneous (SC) injection, Days 1 - 5 of every 28-day cycle
• MGCD0103
90 mg, oral (PO) administration, 3 times per week for 12 doses, 28-day cycle
• MGCD0103
90 mg, oral (PO) administration, 3 times per week for 10 doses, 28-day cycle

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Diamond Centre, Leukemia/BMT Program of BC	Vancouver	British Columbia
United Kingdom	University Hospital	Birmingham
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Kings College Hospital	London
United Kingdom	St. Bartholomews Hospital	London
United Kingdom	John Radcliffe Hospital	Oxford
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate as assessed using IWG criteria for AML and MDS		After 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment	No
Secondary	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		After 45, 90, 135, and 180 subjects are enrolled and evaluated for response to treatment	Yes

External Links

•   The Leukemia & Lymphoma Society
•   The Myelodysplastic Syndromes Foundation