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Myelodysplastic Syndrome (MDS)Phase 2NCT02147873

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

A Phase 2 study testing birinapant and Azacitidine in people with Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by TetraLogic Pharmaceuticals at 76 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
birinapant and Azacitidine
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
118 participants
Where
76 sitesin 4 countries
Study dates
Jun 2014to Jun 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

76 sites in 4 countries.

76 sites in 4 countries

United States46 sites

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • St. Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • University of Maryland, Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • New Jersey Hematology Oncology Associates

    Brick, New Jersey, 08724

  • Gabrail Cancer Center Research

    Canton, Ohio, 44718

  • Medical University of South Carolina, Hollings Cancer Center

    Charleston, South Carolina, 29425

  • Tennessee Oncology

    Chattanooga, Tennessee, 37404

  • Oncology Hematology Care, Inc.

    Cincinnati, Ohio, 45242

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • North Shore Hematology Oncology Associates

    East Setauket, New York, 11733

  • Palo Verde Hematology Oncology

    Glendale, Arizona, 85304

  • Arizona Center for Cancer Care

    Glendale, Arizona, 85306

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Cancer Specialists of North Florida

    Jacksonville, Florida, 32207

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • Monter Cancer Center

    Lake Success, New York, 11042

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90095

  • University of Louisville Hospital/James Graham Brown Cancer Center

    Louisville, Kentucky, 40202

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Tulane Medical Center

    New Orleans, Louisiana, 70112

  • Columbia University Medical Center

    New York, New York, 10032

  • Weill Cornell Medical College - New York-Presbyterian Hospital

    New York, New York, 10065

  • North County Oncology

    Oceanside, California, 92056

  • Hematology Oncology Associates of the Treasure Coast

    Port Saint Lucie, Florida, 34952

  • Oregon Health and Sciences University

    Portland, Oregon, 97239

  • Desert Hematology Oncology Medical Group

    Rancho Mirage, California, 92270

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia, 23298

  • Carolina Blood and Cancer Care Associates, P.A.

    Rock Hill, South Carolina, 29732

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • University of Utah, Huntsman Cancer Hospital

    Salt Lake City, Utah, 84112

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Simmons Cancer Institute at Southern Illinois University

    Springfield, Illinois, 62794

  • Stanford Hospital and Clinics

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Arizona Oncology Associates

    Tucson, Arizona, 85704

  • Tyler Hematology Oncology PA

    Tyler, Texas, 75701

  • Wellness Oncology & Hematology

    West Hills, California, 91307

  • Bond Clinic PA

    Winter Haven, Florida, 33880

  • University of Massachusetts Worcester

    Worcester, Massachusetts, 01655

Other trials in United States

Spain11 sites

  • Hospital Germans Trias I Pujol

    Badalona, Badalona, 08916

  • Hospital University Reina Sofia

    Córdoba, Cordoba, 14004

  • Hospital Clinico Universitario Virgen de la Arrixaca

    El Palmar, Murcia, 30120

  • Hospital Universitario Severo Ochoa

    Leganés, Madrid, 28911

  • Hospital Universitario Gregorio Maranon

    Madrid, Madrid, 28007

  • MD Anderson Cancer Center

    Madrid, Madrid, 28033

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario de Salamanca

    Salamanca, Salamanca, 37007

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna, S/C Tenerife, 38320

  • Complejo Hospitalario Virgen de la Salud

    Toledo, Toledo, 45004

  • Hospital Clinico Universitario de Valencia

    Valencia, Valencia, 46010

Other trials in Spain

Australia10 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • Austin Health

    Heidelberg, Victoria, 3084

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • Cabrini Hospital

    Malvern, Victoria, 3144

  • The Alfred

    Melbourne, Victoria, 3004

  • Perth Blood Institute

    Nedlands, Western Australia, 6009

  • Westmead Hospital

    Westmead, New South Wales, 2145

  • Border Medical Oncology

    Wodonga, Victoria, 3690

  • Metro South Health, Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Germany9 sites

  • University Hospital of Cologne

    Cologne, North Rhine-Westphalia, 50937

  • Marien Hospital Dusseldorf

    Düsseldorf, North Rhine-Westphalia, 40479

  • Universitatsklinikum Essen

    Essen, 45147

  • University Hospital Halle

    Halle, Saxony-Anhalt, 06120

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Medizinische Universitatsklinik Heidelberg

    Heidelberg, 69120

  • Klinikum Rechts der Isar, Technischen Universitat Munchen

    München, Bavaria, 81675

  • Klinikum der Ludwig-Maximilians-Universitat Munchen

    Munich, Bavaria, 81377

  • Universitatsklinikum Wurzburg

    Würzburg, 97080

Other trials in Germany

About this study

Official title: 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

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.

Read the 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.

Being tested
birinapant, Azacitidine, Placebo
Keywords
MDS, CMML, myelodysplastic syndrome, chronic myelomonocytic leukemia, TL32711, TL32711-0094, azacitidine, birinapant, higher risk, naive, double blind, placebo, placebo controlled, randomized
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • birinapantDrug

    Also called TL32711

  • AzacitidineDrug

  • PlaceboDrug

Study groups in NCT02147873
Study groupRoleWhat they receive
azacitidine with birinapantActive 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
Receives: Drug: birinapant; Drug: Azacitidine
Azacitidine and placeboPlacebo 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
Receives: Drug: Azacitidine; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response Rate

    Measured: participants will be followed for until disease progression an expected average of 1 year

Secondary outcomes (7)

  1. Hematologic improvement

    Measured: participants will be followed for until disease progression an expected average of 1 year

  2. Relapse free survival

    According to modified IWG 2006 criteria

    Measured: An expected average of 2 year post last study dose

  3. Time to respond

    Measured: participants will be followed for until disease progression an expected average of 1 year

  4. Change in transfusion requirements

    Measured: participants will be followed for until disease progression an expected average of 1 year

  5. duration of response

    According to modified IWG 2006 criteria

    Measured: participants will be followed for until disease progression an expected average of 1 year

  6. overall survival

    Measured: An expected average of 2 year post last study dose

  7. Adverse events profile

    Measured: participants will be monitored for adverse events throughout the treatment period and during follow up period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2014 (estimated)
  2. Study startJun 2014
  3. Primary completionJan 2016
  4. Study completionJun 2016

Why it stopped: Study terminated due to lack of efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
118 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02147873
Sponsor's protocol ID
TL32711-RAN-0094-PTL
Other IDs
2014-001719-37, 2014
Status last verified
Oct 2016
First submitted
13 May 2014
Last updated
20 Oct 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing birinapant and Azacitidine in people with Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by TetraLogic Pharmaceuticals at 76 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in United States, Spain, Australia, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study terminated due to lack of efficacy). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate (time frame: participants will be followed for until disease progression an expected average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02147873.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2016.

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