Study Stopped
Study terminated due to lack of efficacy
Study of Azacitidine With or Without Birinapant in Subjects With MDS or CMMoL
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Azacitidine With or Without Birinapant With a Single Arm Open-Label Run-In Phase in Subjects With Higher Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
2 other identifiers
interventional
118
4 countries
76
Brief Summary
This is a randomized double blind placebo controlled study of azacitidine with or without birinapant in subjects with higher risk Myelodysplastic syndrome, secondary MDS or myelomonocytic leukemia (CMMoL) who are naïve, to azacitidine therapy. Pre-clinical and mechanistic studies support that azacitidine may modulate pathways that enable birinapant-mediated anti-tumor activity.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2014
76 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2014
CompletedFirst Posted
Study publicly available on registry
May 28, 2014
CompletedStudy Start
First participant enrolled
June 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2016
CompletedOctober 20, 2016
October 1, 2016
1.6 years
May 13, 2014
October 18, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Response Rate
participants will be followed for until disease progression an expected average of 1 year
Secondary Outcomes (7)
Hematologic improvement
participants will be followed for until disease progression an expected average of 1 year
Relapse free survival
An expected average of 2 year post last study dose
Time to respond
participants will be followed for until disease progression an expected average of 1 year
Change in transfusion requirements
participants will be followed for until disease progression an expected average of 1 year
duration of response
participants will be followed for until disease progression an expected average of 1 year
- +2 more secondary outcomes
Other Outcomes (1)
exploratory translational biomarkers for antitumor effect
30 days
Study Arms (2)
azacitidine with birinapant
ACTIVE COMPARATORAzacitidine 75 mg/m2 IV on days 1-5, 8 \& 9 OR days 1-7 and birinapant 13 mg/m2 IV twice a week (days 1 \& 4) for 3 out of 4 weeks
Azacitidine and placebo
PLACEBO COMPARATORAzacitidine 75mg/m2 IV days 1-5, 8 \& 9 OR days 1-7 and placebo IV twice a week (days 1 \& 4) for 3 out of 4 weeks
Interventions
Eligibility Criteria
You may qualify if:
- Morphologically confirmed diagnosis of MDS/CMMoL according to FAB or WHO classification, including RAEB-t and MDS/MPN
- International prognostic score-revised (IPSS-R) of \>3.5 (Intermediate, High or Very High)
- Previously untreated with hypomethylating agents for MDS/CMMoL
- Performance status of 0, 1 or 2 by the ECOG scale
- Adequate renal and liver function
- Female subjects of childbearing potential must have a negative serum pregnancy test at screening within 96 hours prior to the first study dose.
- Female subjects of childbearing potential and male subjects with partners of childbearing potential should ensure use of a highly effective method of birth control as defined by the investigator, for example, those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly during the study and for a period of 3 months following the last dose of any drug administered during the study.
You may not qualify if:
- Relapsed or refractory to hypomethylating agents
- Acute myeloid leukemia (AML), except those patients with RAEB-t who are not candidates for intensive AML therapy.
- Participated in any interventional study within 4 weeks of randomization or 5 half lives (whichever is longer).
- Received any hematopoietic growth factors within 14 days prior to screening.
- Prior malignancy or secondary malignancy within the prior 2 years (except in situ cervical cancer, squamous cell carcinoma or basal cell carcinoma of the skin).
- known diagnosis of human immunodeficiency virus or chronic active Hep B or C.
- Uncontrolled hypertension
- Impaired cardiac function, uncontrolled cardiac arrhythmias despite medications, or clinically significant cardiac disease
- Lack of recovery of prior adverse events to Grade ≤1 severity (National Cancer Institute Common Terminology Criteria for Adverse Events version 4) (except alopecia) due to therapy administered prior to the initiation of study drug dosing.
- Nursing or pregnant.
- Known allergy or hypersensitivity to any of the formulation components
- Any concurrent disease and/or medical condition that, in the opinion of the Investigator, would prevent the subject's participation.
- History of cranial nerve palsy.
- Being treated with anti-TNF therapies or has been treated with an anti-TNF therapy within 5 half-lives of randomization.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (76)
Palo Verde Hematology Oncology
Glendale, Arizona, 85304, United States
Arizona Center for Cancer Care
Glendale, Arizona, 85306, United States
Mayo Clinic
Scottsdale, Arizona, 85259, United States
Arizona Oncology Associates
Tucson, Arizona, 85704, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095, United States
North County Oncology
Oceanside, California, 92056, United States
Desert Hematology Oncology Medical Group
Rancho Mirage, California, 92270, United States
Stanford Hospital and Clinics
Stanford, California, 94305, United States
Wellness Oncology & Hematology
West Hills, California, 91307, United States
Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
Cancer Specialists of North Florida
Jacksonville, Florida, 32207, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Hematology Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612, United States
Bond Clinic PA
Winter Haven, Florida, 33880, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Simmons Cancer Institute at Southern Illinois University
Springfield, Illinois, 62794, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Louisville Hospital/James Graham Brown Cancer Center
Louisville, Kentucky, 40202, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, United States
University of Maryland, Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
University of Massachusetts Worcester
Worcester, Massachusetts, 01655, United States
St. Joseph Mercy Hospital
Ann Arbor, Michigan, 48106, United States
New Jersey Hematology Oncology Associates
Brick, New Jersey, 08724, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
North Shore Hematology Oncology Associates
East Setauket, New York, 11733, United States
Monter Cancer Center
Lake Success, New York, 11042, United States
Columbia University Medical Center
New York, New York, 10032, United States
Weill Cornell Medical College - New York-Presbyterian Hospital
New York, New York, 10065, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Gabrail Cancer Center Research
Canton, Ohio, 44718, United States
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45242, United States
Oregon Health and Sciences University
Portland, Oregon, 97239, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Medical University of South Carolina, Hollings Cancer Center
Charleston, South Carolina, 29425, United States
Carolina Blood and Cancer Care Associates, P.A.
Rock Hill, South Carolina, 29732, United States
Tennessee Oncology
Chattanooga, Tennessee, 37404, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Tyler Hematology Oncology PA
Tyler, Texas, 75701, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
University of Utah, Huntsman Cancer Hospital
Salt Lake City, Utah, 84112, United States
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Metro South Health, Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Austin Health
Heidelberg, Victoria, 3084, Australia
Cabrini Hospital
Malvern, Victoria, 3144, Australia
The Alfred
Melbourne, Victoria, 3004, Australia
Border Medical Oncology
Wodonga, Victoria, 3690, Australia
Perth Blood Institute
Nedlands, Western Australia, 6009, Australia
Klinikum der Ludwig-Maximilians-Universitat Munchen
Munich, Bavaria, 81377, Germany
Klinikum Rechts der Isar, Technischen Universitat Munchen
München, Bavaria, 81675, Germany
University Hospital of Cologne
Cologne, North Rhine-Westphalia, 50937, Germany
Marien Hospital Dusseldorf
Düsseldorf, North Rhine-Westphalia, 40479, Germany
University Hospital Halle
Halle, Saxony-Anhalt, 06120, Germany
Universitatsklinikum Essen
Essen, 45147, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Medizinische Universitatsklinik Heidelberg
Heidelberg, 69120, Germany
Universitatsklinikum Wurzburg
Würzburg, 97080, Germany
Hospital Germans Trias I Pujol
Badalona, Badalona, 08916, Spain
Hospital University Reina Sofia
Córdoba, Cordoba, 14004, Spain
Hospital Universitario Severo Ochoa
Leganés, Madrid, 28911, Spain
Hospital Universitario Gregorio Maranon
Madrid, Madrid, 28007, Spain
MD Anderson Cancer Center
Madrid, Madrid, 28033, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120, Spain
Clinica Universidad de Navarra
Pamplona, Navarre, 31008, Spain
Hospital Universitario de Canarias
San Cristóbal de La Laguna, S/C Tenerife, 38320, Spain
Hospital Universitario de Salamanca
Salamanca, Salamanca, 37007, Spain
Complejo Hospitalario Virgen de la Salud
Toledo, Toledo, 45004, Spain
Hospital Clinico Universitario de Valencia
Valencia, Valencia, 46010, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2014
First Posted
May 28, 2014
Study Start
June 1, 2014
Primary Completion
January 1, 2016
Study Completion
June 1, 2016
Last Updated
October 20, 2016
Record last verified: 2016-10