Study of Azacitidine With or Without Birinapant in Subjects With MDS or CMMoL

NCT ID: NCT02147873

Last Updated: 2016-10-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

118 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-30

Study Completion Date

2016-06-30

Brief Summary

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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

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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.

Conditions

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Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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azacitidine with 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

Group Type ACTIVE_COMPARATOR

birinapant

Intervention Type DRUG

Azacitidine

Intervention Type DRUG

Azacitidine and 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

Group Type PLACEBO_COMPARATOR

Azacitidine

Intervention Type DRUG

Placebo

Intervention Type DRUG

Interventions

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birinapant

Intervention Type DRUG

Azacitidine

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

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TL32711

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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TetraLogic Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Palo Verde Hematology Oncology

Glendale, Arizona, United States

Site Status

Arizona Center for Cancer Care

Glendale, Arizona, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

Arizona Oncology Associates

Tucson, Arizona, United States

Site Status

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Site Status

North County Oncology

Oceanside, California, United States

Site Status

Desert Hematology Oncology Medical Group

Rancho Mirage, California, United States

Site Status

Stanford Hospital and Clinics

Stanford, California, United States

Site Status

Wellness Oncology & Hematology

West Hills, California, United States

Site Status

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

Cancer Specialists of North Florida

Jacksonville, Florida, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Site Status

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Site Status

Bond Clinic PA

Winter Haven, Florida, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Simmons Cancer Institute at Southern Illinois University

Springfield, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Louisville Hospital/James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

University of Maryland, Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

University of Massachusetts Worcester

Worcester, Massachusetts, United States

Site Status

St. Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

New Jersey Hematology Oncology Associates

Brick, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

North Shore Hematology Oncology Associates

East Setauket, New York, United States

Site Status

Monter Cancer Center

Lake Success, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Weill Cornell Medical College - New York-Presbyterian Hospital

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States

Site Status

Oregon Health and Sciences University

Portland, Oregon, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

Carolina Blood and Cancer Care Associates, P.A.

Rock Hill, South Carolina, United States

Site Status

Tennessee Oncology

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Tyler Hematology Oncology PA

Tyler, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Metro South Health, Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Cabrini Hospital

Malvern, Victoria, Australia

Site Status

The Alfred

Melbourne, Victoria, Australia

Site Status

Border Medical Oncology

Wodonga, Victoria, Australia

Site Status

Perth Blood Institute

Nedlands, Western Australia, Australia

Site Status

Klinikum der Ludwig-Maximilians-Universitat Munchen

Munich, Bavaria, Germany

Site Status

Klinikum Rechts der Isar, Technischen Universitat Munchen

München, Bavaria, Germany

Site Status

University Hospital of Cologne

Cologne, North Rhine-Westphalia, Germany

Site Status

Marien Hospital Dusseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Site Status

University Hospital Halle

Halle, Saxony-Anhalt, Germany

Site Status

Universitatsklinikum Essen

Essen, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Medizinische Universitatsklinik Heidelberg

Heidelberg, , Germany

Site Status

Universitatsklinikum Wurzburg

Würzburg, , Germany

Site Status

Hospital Germans Trias I Pujol

Badalona, Badalona, Spain

Site Status

Hospital University Reina Sofia

Córdoba, Cordoba, Spain

Site Status

Hospital Universitario Severo Ochoa

Leganés, Madrid, Spain

Site Status

Hospital Universitario Gregorio Maranon

Madrid, Madrid, Spain

Site Status

MD Anderson Cancer Center

Madrid, Madrid, Spain

Site Status

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Site Status

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital Universitario de Canarias

San Cristóbal de La Laguna, S/C Tenerife, Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, Salamanca, Spain

Site Status

Complejo Hospitalario Virgen de la Salud

Toledo, Toledo, Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, Valencia, Spain

Site Status

Countries

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United States Australia Germany Spain

Other Identifiers

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2014-001719-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TL32711-RAN-0094-PTL

Identifier Type: -

Identifier Source: org_study_id

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