Study of Azacitidine With or Without Birinapant in Subjects With MDS or CMMoL
- Conditions
- Myelodysplastic Syndrome (MDS)Chronic Myelomonocytic Leukemia (CMML)
- Interventions
- Registration Number
- NCT02147873
- Lead Sponsor
- TetraLogic Pharmaceuticals
- 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.
- Detailed Description
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)
The primary purpose of this study is :
-To compare the relative effect of azacitidine plus birinapant versus azacitidine plus placebo on response rate in patients with higher-risk MDS, secondary MDS or CMMoL.
The secondary purpose of this study is to compare effect of azacitidine plus birinapant relative to azacitidine with placebo on:
* Hematologic improvement
* Relapse free survival
* Time to respond
* Change in transfusion requirements
* Duration of response
* Overall survival
* Adverse events
The exploratory objective of this study is to assess exploratory translational biomarkers for antitumor effects.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 118
- 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.
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description azacitidine with birinapant birinapant Azacitidine 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 Azacitidine Azacitidine 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 Azacitidine and placebo Placebo Azacitidine 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 azacitidine with birinapant Azacitidine Azacitidine 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
- Primary Outcome Measures
Name Time Method Response Rate participants will be followed for until disease progression an expected average of 1 year
- Secondary Outcome Measures
Name Time Method 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 According to modified IWG 2006 criteria
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 According to modified IWG 2006 criteria
overall survival An expected average of 2 year post last study dose Adverse events profile participants will be monitored for adverse events throughout the treatment period and during follow up period
Trial Locations
- Locations (75)
University of Maryland, Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Desert Hematology Oncology Medical Group
🇺🇸Rancho Mirage, California, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Murcia, Spain
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Utah, Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
Arizona Center for Cancer Care
🇺🇸Glendale, Arizona, United States
Wellness Oncology & Hematology
🇺🇸West Hills, California, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Simmons Cancer Institute at Southern Illinois University
🇺🇸Springfield, Illinois, United States
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
Hematology Oncology Associates of the Treasure Coast
🇺🇸Port St. Lucie, Florida, United States
Palo Verde Hematology Oncology
🇺🇸Glendale, Arizona, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Bond Clinic PA
🇺🇸Winter Haven, Florida, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
North County Oncology
🇺🇸Oceanside, California, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
North Shore Hematology Oncology Associates
🇺🇸East Setauket, New York, United States
University of Massachusetts Worcester
🇺🇸Worcester, Massachusetts, United States
New Jersey Hematology Oncology Associates
🇺🇸Brick, New Jersey, United States
Weill Cornell Medical College - New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Metro South Health, Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Border Medical Oncology
🇦🇺Wodonga, Victoria, Australia
Universitatsklinikum Essen
🇩🇪Essen, Germany
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Cabrini Hospital
🇦🇺Malvern, Victoria, Australia
Perth Blood Institute
🇦🇺Nedlands, Western Australia, Australia
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Germans Trias I Pujol
🇪🇸Badalona, Spain
Complejo Hospitalario Virgen de la Salud
🇪🇸Toledo, Spain
Hospital University Reina Sofia
🇪🇸Cordoba, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Universitatsklinikum Wurzburg
🇩🇪Wurzburg, Germany
Monter Cancer Center
🇺🇸Lake Success, New York, United States
Medical University of South Carolina, Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Tyler Hematology Oncology PA
🇺🇸Tyler, Texas, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
The Alfred
🇦🇺Melbourne, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Klinikum Rechts der Isar, Technischen Universitat Munchen
🇩🇪Munchen, Bayern, Germany
Marien Hospital Dusseldorf
🇩🇪Dusseldorf, Nordrhein-Westfalen, Germany
Klinikum der Ludwig-Maximilians-Universitat Munchen
🇩🇪Munich, Bayern, Germany
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
University Hospital Halle
🇩🇪Halle (Saale), Saxony-Anhalt, Germany
Medizinische Universitatsklinik Heidelberg
🇩🇪Heidelberg, Germany
Hospital Universitario de Canarias
🇪🇸La Laguna, S/C Tenerife, Spain
Hospital Universitario Severo Ochoa
🇪🇸Leganes, Madrid, Spain
University Hospital of Cologne
🇩🇪Cologne, North Rhine Westphalia, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Carolina Blood and Cancer Care Associates, P.A.
🇺🇸Rock Hill, South Carolina, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
University of Louisville Hospital/James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Oregon Health and Sciences University
🇺🇸Portland, Oregon, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States