A Study of MBG453 in Combination With Hypomethylating Agents in Subjects With IPSS-R Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS).

A Randomized, Double-blind, Placebo-controlled Phase II Multi-center Study of Intravenous MBG453 Added to Hypomethylating Agents in Adult Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria

ClinicalTrials.gov Identifier: NCT03946670

Novartis Reference Number: CMBG453B12201

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This Phase II is a multicenter, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to hypomethylating agents (azacitidine or decitabine) in adult subjects with IPSS-R intermediate, high or very high risk myelodysplastic syndrome (MDS) not eligible for Hematopoietic Stem Cell Transplant (HSCT) or intensive chemotherapy.

Condition 
Myelodysplastic Syndromes
Phase 
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
127 participants
Start date 
Jun 04, 2019
Completion date 
Aug 10, 2024
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
MBG453
MBG453 will be administered i.v.
Drug
Placebo
Placebo will be administered i.v.
Drug
Hypomethylating agents
Decitabine will be administered i.v. Azacitidine will be administered i.v or s.c.

Eligibility Criteria

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study.
Age ≥ 18 years at the date of signing the informed consent form (ICF)

Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) by investigator assessment with one of the following Prognostic Risk Categories, based on the International Prognostic Scoring System (IPSS-R):

Very high
High
Intermediate with at least ≥ 5% bone marrow blast
Not eligible at the time of screening, for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions
Not eligible at the time of screening, for hematopoietic stem-cell transplantation (HSCT) according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria:

Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines are allowed except if the drug was administered within 4 months prior to randomization.
Previous first-line treatment for higher risk MDS with chemotherapy or any other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine.
History of severe hypersensitivity reactions to any ingredient of the study treatment (azacitidine, decitabine or MGB453) or their excipients, or to monoclonal antibodies (mAbs).
Currently using or used within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion are allowed and not considered a form of systemic treatment.
Investigational treatment for MDS received within 4 weeks prior to randomization. In case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is necessary to allow enrollment.
Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
Live vaccine administered within 30 Days prior to randomization.

Other protocol-defined Inclusion/Exclusion may apply.

Study Locations

United States
City of Hope National Medical Center Medical Oncology & Therapeutic
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Duarte, 91010
California
United States
Yale University School of Medicine
-
New Haven, 06520
Connecticut
United States
Dana Farber Cancer Institute Centerfor Sarcoma&BoneOncology
-
Boston, 02215
Massachusetts
United States
The Cancer Institute of New Jersey The Cancer Institute of NJ
-
New Brunswick, 08901
New Jersey
United States
Ohio State Comprehensive Cancer Center/James Cancer Hospital SC- BCL201X2102C
-
Columbus, 73210
Ohio
United States
Mary Crowley Cancer Research
-
Dallas, 75251
Texas
United States
Austria
Novartis Investigative Site
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Vienna, 1140
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Austria
Belgium
Novartis Investigative Site
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Brasschaat, 2930
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Belgium
Novartis Investigative Site
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Leuven, 3000
-
Belgium
Canada
Novartis Investigative Site
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Toronto, M5G 1Z6
Ontario
Canada
Novartis Investigative Site
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Quebec, G1J 1Z4
-
Canada
Czechia
Novartis Investigative Site
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Brno - Bohunice, 639 01
-
Czechia
Novartis Investigative Site
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Praha, 12808
-
Czechia
France
Novartis Investigative Site
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Toulouse, 31059
-
France
Germany
Novartis Investigative Site
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Berlin, 13353
-
Germany
Novartis Investigative Site
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Leipzig, 04103
-
Germany
Greece
Novartis Investigative Site
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Alexandroupolis, 681 00
Evros
Greece
Novartis Investigative Site
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Larissa, 411 10
GR
Greece
Novartis Investigative Site
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Patras, 265 00
-
Greece
Hong Kong
Novartis Investigative Site
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Hong Kong,
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Hong Kong
Hungary
Novartis Investigative Site
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Debrecen, 4032
-
Hungary
Novartis Investigative Site
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Nyiregyhaza, 4400
-
Hungary
Italy
Novartis Investigative Site
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Firenze, 50134
FI
Italy
Novartis Investigative Site
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Milano, 20162
MI
Italy
Novartis Investigative Site
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Rozzano, 20089
MI
Italy
Novartis Investigative Site
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Reggio Calabria, 89124
RC
Italy
Novartis Investigative Site
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Roma, 00133
RM
Italy
Japan
Novartis Investigative Site
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Fukuoka city, 812-8582
Fukuoka
Japan
Novartis Investigative Site
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Fukushima city, 960 1295
Fukushima
Japan
Novartis Investigative Site
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Gifu shi, 500 8513
Gifu
Japan
Novartis Investigative Site
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Isehara, 259-1193
Kanagawa
Japan
Novartis Investigative Site
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Sendai-shi, 983 8520
Miyagi
Japan
Novartis Investigative Site
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Nagasaki-city, 852-8501
Nagasaki
Japan
Novartis Investigative Site
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Bunkyo ku, 113-8677
Tokyo
Japan
Novartis Investigative Site
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Kumamoto, 860-0008
-
Japan
Novartis Investigative Site
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Osaka, 545-8586
-
Japan
Korea, Republic of
Novartis Investigative Site
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Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
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Seoul, 06351
-
Korea, Republic of
Spain
Novartis Investigative Site
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Malaga, 29010
Andalucia
Spain
Novartis Investigative Site
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Santander, 39008
Cantabria
Spain
Novartis Investigative Site
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Hospitalet de LLobregat, 08907
Catalunya
Spain
Taiwan
Novartis Investigative Site
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Kaohsiung City, 83301
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Taiwan
Novartis Investigative Site
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Taipei, 10002
-
Taiwan
Turkey
Novartis Investigative Site
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Izmir, 35040
-
Turkey
Novartis Investigative Site
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Kocaeli, 41380
-
Turkey
Novartis Investigative Site
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Samsun, 55139
-
Turkey
United Kingdom
Novartis Investigative Site
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Manchester, M20 4BX
-
United Kingdom

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