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

Sponsor

TetraLogic Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT02147873

Collaborator

(none)

118

Enrollment

Locations

Arms

Duration (Months)

1.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML)	Drug: birinapant Drug: Azacitidine Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

118 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Jan 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: birinapant Other Names: TL32711 Drug: Azacitidine
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	Drug: Azacitidine Drug: Placebo

Arm

Intervention/Treatment

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

Drug: birinapant

Other Names:

TL32711

Drug: Azacitidine

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

Drug: Azacitidine

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Response Rate [participants will be followed for until disease progression an expected average of 1 year]

Secondary Outcome Measures

Hematologic improvement [participants will be followed for until disease progression an expected average of 1 year]
Relapse free survival [An expected average of 2 year post last study dose]
According to modified IWG 2006 criteria
Time to respond [participants will be followed for until disease progression an expected average of 1 year]
Change in transfusion requirements [participants will be followed for until disease progression an expected average of 1 year]
duration of response [participants will be followed for until disease progression an expected average of 1 year]
According to modified IWG 2006 criteria
overall survival [An expected average of 2 year post last study dose]
Adverse events profile [participants will be monitored for adverse events throughout the treatment period and during follow up period]

Other Outcome Measures

exploratory translational biomarkers for antitumor effect [30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Palo Verde Hematology Oncology	Glendale	Arizona	United States	85304
2	Arizona Center for Cancer Care	Glendale	Arizona	United States	85306
3	Mayo Clinic	Scottsdale	Arizona	United States	85259
4	Arizona Oncology Associates	Tucson	Arizona	United States	85704
5	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
6	North County Oncology	Oceanside	California	United States	92056
7	Desert Hematology Oncology Medical Group	Rancho Mirage	California	United States	92270
8	Stanford Hospital and Clinics	Stanford	California	United States	94305
9	Wellness Oncology & Hematology	West Hills	California	United States	91307
10	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
11	Cancer Specialists of North Florida	Jacksonville	Florida	United States	32207
12	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
13	Hematology Oncology Associates of the Treasure Coast	Port St. Lucie	Florida	United States	34952
14	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
15	Bond Clinic PA	Winter Haven	Florida	United States	33880
16	Loyola University Medical Center	Maywood	Illinois	United States	60153
17	Simmons Cancer Institute at Southern Illinois University	Springfield	Illinois	United States	62794
18	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
19	University of Louisville Hospital/James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
20	Tulane Medical Center	New Orleans	Louisiana	United States	70112
21	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
22	University of Massachusetts Worcester	Worcester	Massachusetts	United States	01655
23	St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
24	New Jersey Hematology Oncology Associates	Brick	New Jersey	United States	08724
25	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
26	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
27	Montefiore Medical Center	Bronx	New York	United States	10461
28	North Shore Hematology Oncology Associates	East Setauket	New York	United States	11733
29	Monter Cancer Center	Lake Success	New York	United States	11042
30	Columbia University Medical Center	New York	New York	United States	10032
31	Weill Cornell Medical College - New York-Presbyterian Hospital	New York	New York	United States	10065
32	Duke University Medical Center	Durham	North Carolina	United States	27710
33	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
34	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45242
35	Oregon Health and Sciences University	Portland	Oregon	United States	97239
36	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
37	Medical University of South Carolina, Hollings Cancer Center	Charleston	South Carolina	United States	29425
38	Carolina Blood and Cancer Care Associates, P.A.	Rock Hill	South Carolina	United States	29732
39	Tennessee Oncology	Chattanooga	Tennessee	United States	37404
40	Tennessee Oncology	Nashville	Tennessee	United States	37203
41	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
42	Tyler Hematology Oncology PA	Tyler	Texas	United States	75701
43	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
44	University of Utah, Huntsman Cancer Hospital	Salt Lake City	Utah	United States	84112
45	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298
46	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
47	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
48	Westmead Hospital	Westmead	New South Wales	Australia	2145
49	Metro South Health, Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
50	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
51	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
52	Austin Health	Heidelberg	Victoria	Australia	3084
53	Cabrini Hospital	Malvern	Victoria	Australia	3144
54	The Alfred	Melbourne	Victoria	Australia	3004
55	Border Medical Oncology	Wodonga	Victoria	Australia	3690
56	Perth Blood Institute	Nedlands	Western Australia	Australia	6009
57	Klinikum Rechts der Isar, Technischen Universitat Munchen	Munchen	Bayern	Germany	81675
58	Klinikum der Ludwig-Maximilians-Universitat Munchen	Munich	Bayern	Germany	81377
59	Marien Hospital Dusseldorf	Dusseldorf	Nordrhein-Westfalen	Germany	40479
60	University Hospital of Cologne	Cologne	North Rhine Westphalia	Germany	50937
61	University Hospital Halle	Halle (Saale)	Saxony-Anhalt	Germany	06120
62	Universitatsklinikum Essen	Essen		Germany	45147
63	Medizinische Hochschule Hannover	Hannover		Germany	30625
64	Medizinische Universitatsklinik Heidelberg	Heidelberg		Germany	69120
65	Universitatsklinikum Wurzburg	Wurzburg		Germany	97080
66	Hospital Universitario Severo Ochoa	Leganes	Madrid	Spain	28911
67	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia	Spain	30120
68	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
69	Hospital Universitario de Canarias	La Laguna	S/C Tenerife	Spain	38320
70	Hospital Germans Trias I Pujol	Badalona		Spain	08916
71	Hospital University Reina Sofia	Cordoba		Spain	14004
72	Hospital Universitario Gregorio Maranon	Madrid		Spain	28007
73	MD Anderson Cancer Center	Madrid		Spain	28033
74	Hospital Universitario de Salamanca	Salamanca		Spain	37007
75	Complejo Hospitalario Virgen de la Salud	Toledo		Spain	45004
76	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010