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

Primary Purpose

Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
birinapant
Azacitidine
Placebo
Sponsored by
TetraLogic Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome (MDS) focused on measuring MDS, CMML, myelodysplastic syndrome, chronic myelomonocytic leukemia, TL32711, TL32711-0094, azacitidine, birinapant, higher risk, naive, double blind, placebo, placebo controlled, randomized

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Palo Verde Hematology Oncology
  • Arizona Center for Cancer Care
  • Mayo Clinic
  • Arizona Oncology Associates
  • Ronald Reagan UCLA Medical Center
  • North County Oncology
  • Desert Hematology Oncology Medical Group
  • Stanford Hospital and Clinics
  • Wellness Oncology & Hematology
  • Colorado Blood Cancer Institute
  • Cancer Specialists of North Florida
  • Mayo Clinic Jacksonville
  • Hematology Oncology Associates of the Treasure Coast
  • H. Lee Moffitt Cancer Center & Research Institute
  • Bond Clinic PA
  • Loyola University Medical Center
  • Simmons Cancer Institute at Southern Illinois University
  • University of Iowa Hospitals and Clinics
  • University of Louisville Hospital/James Graham Brown Cancer Center
  • Tulane Medical Center
  • University of Maryland, Greenebaum Cancer Center
  • University of Massachusetts Worcester
  • St. Joseph Mercy Hospital
  • New Jersey Hematology Oncology Associates
  • Hackensack University Medical Center
  • University of New Mexico Cancer Center
  • Montefiore Medical Center
  • North Shore Hematology Oncology Associates
  • Monter Cancer Center
  • Columbia University Medical Center
  • Weill Cornell Medical College - New York-Presbyterian Hospital
  • Duke University Medical Center
  • Gabrail Cancer Center Research
  • Oncology Hematology Care, Inc.
  • Oregon Health and Sciences University
  • Penn State Milton S. Hershey Medical Center
  • Medical University of South Carolina, Hollings Cancer Center
  • Carolina Blood and Cancer Care Associates, P.A.
  • Tennessee Oncology
  • Tennessee Oncology
  • The University of Texas MD Anderson Cancer Center
  • Tyler Hematology Oncology PA
  • Utah Cancer Specialists
  • University of Utah, Huntsman Cancer Hospital
  • Virginia Commonwealth University Massey Cancer Center
  • Seattle Cancer Care Alliance
  • Royal Prince Alfred Hospital
  • Westmead Hospital
  • Metro South Health, Princess Alexandra Hospital
  • Royal Adelaide Hospital
  • Royal Hobart Hospital
  • Austin Health
  • Cabrini Hospital
  • The Alfred
  • Border Medical Oncology
  • Perth Blood Institute
  • Klinikum Rechts der Isar, Technischen Universitat Munchen
  • Klinikum der Ludwig-Maximilians-Universitat Munchen
  • Marien Hospital Dusseldorf
  • University Hospital of Cologne
  • University Hospital Halle
  • Universitatsklinikum Essen
  • Medizinische Hochschule Hannover
  • Medizinische Universitatsklinik Heidelberg
  • Universitatsklinikum Wurzburg
  • Hospital Universitario Severo Ochoa
  • Hospital Clinico Universitario Virgen de la Arrixaca
  • Clinica Universidad de Navarra
  • Hospital Universitario de Canarias
  • Hospital Germans Trias I Pujol
  • Hospital University Reina Sofia
  • Hospital Universitario Gregorio Maranon
  • MD Anderson Cancer Center
  • Hospital Universitario de Salamanca
  • Complejo Hospitalario Virgen de la Salud
  • Hospital Clinico Universitario de Valencia

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

azacitidine with birinapant

Azacitidine and placebo

Arm Description

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 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

Outcomes

Primary Outcome Measures

Response Rate

Secondary Outcome Measures

Hematologic improvement
Relapse free survival
According to modified IWG 2006 criteria
Time to respond
Change in transfusion requirements
duration of response
According to modified IWG 2006 criteria
overall survival
Adverse events profile

Full Information

First Posted
May 13, 2014
Last Updated
October 18, 2016
Sponsor
TetraLogic Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02147873
Brief Title
Study of Azacitidine With or Without Birinapant in Subjects With MDS or CMMoL
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Terminated
Why Stopped
Study terminated due to lack of efficacy
Study Start Date
June 2014 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TetraLogic Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)
Keywords
MDS, CMML, myelodysplastic syndrome, chronic myelomonocytic leukemia, TL32711, TL32711-0094, azacitidine, birinapant, higher risk, naive, double blind, placebo, placebo controlled, randomized

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
azacitidine with birinapant
Arm Type
Active Comparator
Arm Description
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
Arm Title
Azacitidine and placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
birinapant
Other Intervention Name(s)
TL32711
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Response Rate
Time Frame
participants will be followed for until disease progression an expected average of 1 year
Secondary Outcome Measure Information:
Title
Hematologic improvement
Time Frame
participants will be followed for until disease progression an expected average of 1 year
Title
Relapse free survival
Description
According to modified IWG 2006 criteria
Time Frame
An expected average of 2 year post last study dose
Title
Time to respond
Time Frame
participants will be followed for until disease progression an expected average of 1 year
Title
Change in transfusion requirements
Time Frame
participants will be followed for until disease progression an expected average of 1 year
Title
duration of response
Description
According to modified IWG 2006 criteria
Time Frame
participants will be followed for until disease progression an expected average of 1 year
Title
overall survival
Time Frame
An expected average of 2 year post last study dose
Title
Adverse events profile
Time Frame
participants will be monitored for adverse events throughout the treatment period and during follow up period
Other Pre-specified Outcome Measures:
Title
exploratory translational biomarkers for antitumor effect
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Palo Verde Hematology Oncology
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85304
Country
United States
Facility Name
Arizona Center for Cancer Care
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85306
Country
United States
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Arizona Oncology Associates
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
North County Oncology
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
Facility Name
Desert Hematology Oncology Medical Group
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Facility Name
Stanford Hospital and Clinics
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Wellness Oncology & Hematology
City
West Hills
State/Province
California
ZIP/Postal Code
91307
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Cancer Specialists of North Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Hematology Oncology Associates of the Treasure Coast
City
Port St. Lucie
State/Province
Florida
ZIP/Postal Code
34952
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Bond Clinic PA
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Simmons Cancer Institute at Southern Illinois University
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62794
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Louisville Hospital/James Graham Brown Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Tulane Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Maryland, Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Massachusetts Worcester
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
St. Joseph Mercy Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
New Jersey Hematology Oncology Associates
City
Brick
State/Province
New Jersey
ZIP/Postal Code
08724
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
North Shore Hematology Oncology Associates
City
East Setauket
State/Province
New York
ZIP/Postal Code
11733
Country
United States
Facility Name
Monter Cancer Center
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Weill Cornell Medical College - New York-Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Oncology Hematology Care, Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Oregon Health and Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Medical University of South Carolina, Hollings Cancer Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Carolina Blood and Cancer Care Associates, P.A.
City
Rock Hill
State/Province
South Carolina
ZIP/Postal Code
29732
Country
United States
Facility Name
Tennessee Oncology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Tyler Hematology Oncology PA
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
University of Utah, Huntsman Cancer Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Virginia Commonwealth University Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Metro South Health, Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Cabrini Hospital
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Facility Name
The Alfred
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Border Medical Oncology
City
Wodonga
State/Province
Victoria
ZIP/Postal Code
3690
Country
Australia
Facility Name
Perth Blood Institute
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Klinikum Rechts der Isar, Technischen Universitat Munchen
City
Munchen
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
Klinikum der Ludwig-Maximilians-Universitat Munchen
City
Munich
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
Facility Name
Marien Hospital Dusseldorf
City
Dusseldorf
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
40479
Country
Germany
Facility Name
University Hospital of Cologne
City
Cologne
State/Province
North Rhine Westphalia
ZIP/Postal Code
50937
Country
Germany
Facility Name
University Hospital Halle
City
Halle (Saale)
State/Province
Saxony-Anhalt
ZIP/Postal Code
06120
Country
Germany
Facility Name
Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Medizinische Universitatsklinik Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitatsklinikum Wurzburg
City
Wurzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Hospital Universitario Severo Ochoa
City
Leganes
State/Province
Madrid
ZIP/Postal Code
28911
Country
Spain
Facility Name
Hospital Clinico Universitario Virgen de la Arrixaca
City
El Palmar
State/Province
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Universitario de Canarias
City
La Laguna
State/Province
S/C Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
Hospital Germans Trias I Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital University Reina Sofia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
MD Anderson Cancer Center
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Complejo Hospitalario Virgen de la Salud
City
Toledo
ZIP/Postal Code
45004
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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