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

Myelodysplastic Syndrome (MDS) Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02147873
• Other study ID #: TL32711-RAN-0094-PTL
• Secondary ID: 2014-001719-37
• Status: Terminated
• Phase: Phase 2
• First received: May 13, 2014
• Last updated: October 18, 2016
• Start date: June 2014
• Est. completion date: June 2016

Study information

• Verified date: October 2016
• Source: TetraLogic Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationGermany: Federal Institute for Drugs and Medical DevicesSpain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical 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. Pre-clinical and mechanistic studies support that azacitidine may modulate pathways that enable birinapant-mediated anti-tumor activity.

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 information / eligibility

• Status: Terminated
• Enrollment: 118
• Est. completion date: June 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

key 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.

Key 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia (CMML)
• Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• birinapant

• Azacitidine

• Placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Cabrini Hospital	Malvern	Victoria
Australia	The Alfred	Melbourne	Victoria
Australia	Perth Blood Institute	Nedlands	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Border Medical Oncology	Wodonga	Victoria
Australia	Metro South Health, Princess Alexandra Hospital	Woolloongabba	Queensland
Germany	University Hospital of Cologne	Cologne	North Rhine Westphalia
Germany	Marien Hospital Dusseldorf	Dusseldorf	Nordrhein-Westfalen
Germany	Universitatsklinikum Essen	Essen
Germany	University Hospital Halle	Halle (Saale)	Saxony-Anhalt
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Medizinische Universitatsklinik Heidelberg	Heidelberg
Germany	Klinikum Rechts der Isar, Technischen Universitat Munchen	Munchen	Bayern
Germany	Klinikum der Ludwig-Maximilians-Universitat Munchen	Munich	Bayern
Germany	Universitatsklinikum Wurzburg	Wurzburg
Spain	Hospital Germans Trias I Pujol	Badalona
Spain	Hospital University Reina Sofia	Cordoba
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital Universitario de Canarias	La Laguna	S/C Tenerife
Spain	Hospital Universitario Severo Ochoa	Leganes	Madrid
Spain	Hospital Universitario Gregorio Maranon	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Complejo Hospitalario Virgen de la Salud	Toledo
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland
United States	New Jersey Hematology Oncology Associates	Brick	New Jersey
United States	Montefiore Medical Center	Bronx	New York
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Medical University of South Carolina, Hollings Cancer Center	Charleston	South Carolina
United States	Tennessee Oncology	Chattanooga	Tennessee
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	North Shore Hematology Oncology Associates	East Setauket	New York
United States	Arizona Center for Cancer Care	Glendale	Arizona
United States	Palo Verde Hematology Oncology	Glendale	Arizona
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Monter Cancer Center	Lake Success	New York
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Louisville Hospital/James Graham Brown Cancer Center	Louisville	Kentucky
United States	Loyola University Medical Center	Maywood	Illinois
United States	Tennessee Oncology	Nashville	Tennessee
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Weill Cornell Medical College - New York-Presbyterian Hospital	New York	New York
United States	North County Oncology	Oceanside	California
United States	Hematology Oncology Associates of the Treasure Coast	Port St. Lucie	Florida
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Desert Hematology Oncology Medical Group	Rancho Mirage	California
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Carolina Blood and Cancer Care Associates, P.A.	Rock Hill	South Carolina
United States	University of Utah, Huntsman Cancer Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Mayo Clinic	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Simmons Cancer Institute at Southern Illinois University	Springfield	Illinois
United States	Stanford Hospital and Clinics	Stanford	California
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Tyler Hematology Oncology PA	Tyler	Texas
United States	Wellness Oncology & Hematology	West Hills	California
United States	Bond Clinic PA	Winter Haven	Florida
United States	University of Massachusetts Worcester	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
TetraLogic Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	exploratory translational biomarkers for antitumor effect		30 days	No
Primary	Response Rate		participants will be followed for until disease progression an expected average of 1 year	No
Secondary	Hematologic improvement		participants will be followed for until disease progression an expected average of 1 year	No
Secondary	Relapse free survival	According to modified IWG 2006 criteria	An expected average of 2 year post last study dose	No
Secondary	Time to respond		participants will be followed for until disease progression an expected average of 1 year	No
Secondary	Change in transfusion requirements		participants will be followed for until disease progression an expected average of 1 year	No
Secondary	duration of response	According to modified IWG 2006 criteria	participants will be followed for until disease progression an expected average of 1 year	No
Secondary	overall survival		An expected average of 2 year post last study dose	No
Secondary	Adverse events profile		participants will be monitored for adverse events throughout the treatment period and during follow up period	Yes