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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02147873




Registration number
NCT02147873
Ethics application status
Date submitted
13/05/2014
Date registered
28/05/2014
Date last updated
20/10/2016

Titles & IDs
Public title
Study of Azacitidine With or Without Birinapant in Subjects With MDS or CMMoL
Scientific 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
Secondary ID [1] 0 0
2014-001719-37
Secondary ID [2] 0 0
TL32711-RAN-0094-PTL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndrome (MDS) 0 0
Chronic Myelomonocytic Leukemia (CMML) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active comparator: 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

Placebo comparator: 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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Response Rate
Timepoint [1] 0 0
participants will be followed for until disease progression an expected average of 1 year
Secondary outcome [1] 0 0
Hematologic improvement
Timepoint [1] 0 0
participants will be followed for until disease progression an expected average of 1 year
Secondary outcome [2] 0 0
Relapse free survival
Timepoint [2] 0 0
An expected average of 2 year post last study dose
Secondary outcome [3] 0 0
Time to respond
Timepoint [3] 0 0
participants will be followed for until disease progression an expected average of 1 year
Secondary outcome [4] 0 0
Change in transfusion requirements
Timepoint [4] 0 0
participants will be followed for until disease progression an expected average of 1 year
Secondary outcome [5] 0 0
duration of response
Timepoint [5] 0 0
participants will be followed for until disease progression an expected average of 1 year
Secondary outcome [6] 0 0
overall survival
Timepoint [6] 0 0
An expected average of 2 year post last study dose
Secondary outcome [7] 0 0
Adverse events profile
Timepoint [7] 0 0
participants will be monitored for adverse events throughout the treatment period and during follow up period

Eligibility
Key inclusion criteria
key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2016
Sample size
Target
Accrual to date
Final
118
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Metro South Health, Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [8] 0 0
The Alfred - Melbourne
Recruitment hospital [9] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [10] 0 0
Perth Blood Institute - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3144 - Malvern
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
3690 - Wodonga
Recruitment postcode(s) [10] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New Mexico
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
Germany
State/province [25] 0 0
Bayern
Country [26] 0 0
Germany
State/province [26] 0 0
Nordrhein-Westfalen
Country [27] 0 0
Germany
State/province [27] 0 0
North Rhine Westphalia
Country [28] 0 0
Germany
State/province [28] 0 0
Saxony-Anhalt
Country [29] 0 0
Germany
State/province [29] 0 0
Essen
Country [30] 0 0
Germany
State/province [30] 0 0
Hannover
Country [31] 0 0
Germany
State/province [31] 0 0
Heidelberg
Country [32] 0 0
Germany
State/province [32] 0 0
Wurzburg
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Murcia
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Spain
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Navarra
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Spain
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S/C Tenerife
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Spain
State/province [37] 0 0
Badalona
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Spain
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Cordoba
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Spain
State/province [39] 0 0
Salamanca
Country [40] 0 0
Spain
State/province [40] 0 0
Toledo
Country [41] 0 0
Spain
State/province [41] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
TetraLogic Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02147873
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02147873