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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)

Primary Purpose

Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Azacitidine
MGCD0103
MGCD0103
Sponsored by
Mirati Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Acute Myeloid Leukemia, Myelodysplastic Syndrome, Azacitidine, Vidaza, MGCD0103, Histone deacetylase inhibitor, DNA methyltransferase inhibitor, Epigenetic Therapy

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • MD Anderson Cancer Center
  • Diamond Centre, Leukemia/BMT Program of BC
  • Jewish General Hospital
  • University Hospital
  • Royal Bournemouth Hospital
  • St. Bartholomews Hospital
  • Kings College Hospital
  • John Radcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

A

B

C

Arm Description

Azacitidine

MGCD0103

Azacitidine + MGCD0103

Outcomes

Primary Outcome Measures

Overall response rate as assessed using IWG criteria for AML and MDS

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

Full Information

First Posted
April 23, 2008
Last Updated
April 22, 2015
Sponsor
Mirati Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00666497
Brief Title
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

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Terminated
Why Stopped
Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 with be closed.
Study Start Date
June 2008 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirati Therapeutics Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
Keywords
Acute Myeloid Leukemia, Myelodysplastic Syndrome, Azacitidine, Vidaza, MGCD0103, Histone deacetylase inhibitor, DNA methyltransferase inhibitor, Epigenetic Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Azacitidine
Arm Title
B
Arm Type
Experimental
Arm Description
MGCD0103
Arm Title
C
Arm Type
Experimental
Arm Description
Azacitidine + MGCD0103
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
75 mg/m2/day for 5 days, subcutaneous (SC) injection, Days 1 - 5 of every 28-day cycle
Intervention Type
Drug
Intervention Name(s)
MGCD0103
Intervention Description
90 mg, oral (PO) administration, 3 times per week for 12 doses, 28-day cycle
Intervention Type
Drug
Intervention Name(s)
MGCD0103
Intervention Description
90 mg, oral (PO) administration, 3 times per week for 10 doses, 28-day cycle
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Reid, MSc, MBA
Organizational Affiliation
MethylGene Inc.
Official's Role
Study Director
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Diamond Centre, Leukemia/BMT Program of BC
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E3
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
University Hospital
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
St. Bartholomews Hospital
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
Kings College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://www.leukemia-lymphoma.org/hm_lls
Description
The Leukemia & Lymphoma Society
URL
http://www.mds-foundation.org/
Description
The Myelodysplastic Syndromes Foundation

Learn more about this trial

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

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