Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)

A Randomized, Double-blind, Placebo-controlled Phase III Multi-center Study of Azacitidine With or Without MBG453 for the Treatment of Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)

ClinicalTrials.gov Identifier: NCT04266301

Novartis Reference Number: CMBG453B12301

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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 is a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult subjects with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who have an indication for treatment with azacitidine in first-line setting and are not eligible for intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) according to medical judgment by the investigator.

The purpose of the current study is to assess clinical effects of MBG453 in combination with azacitidine in adult subjects with IPSS-R intermediate, high, very high risk MDS and CMML-2.

Condition 
Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
500 participants
Start date 
Jun 08, 2020
Completion date 
Aug 26, 2027
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
MBG453
A dose of MBG453 800 mg will be administered intravenously (IV) every 4 weeks (Q4W).
Drug
Azacitidine
A dose of Azacitidine 75 mg/m2 will be administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.
Drug
Placebo
A dose of Placebo 800 mg will be administered intravenously every 4 weeks (Q4W).

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

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

Very high (> 6 points)
High (> 4.5 - ≤ 6 points)
Intermediate (> 3 - ≤ 4.5 points) Or Morphologically confirmed diagnosis of Chronic Myelomonocytic Leukemia -2 based on WHO 2016 classification (Arber et al 2016) by local investigator assessment with WBC < 13 x 109/L
Indication for azacitidine treatment according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions
Not eligible at time of screening for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions, including assessment of individual clinical factors such as age, comorbidities and performance status
Not eligible at 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, including assessment of individual clinical factors such as age, comorbidities, performance status, and donor availability
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 checkpoint inhibitors (e.g, anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines is allowed except if the drug was administered within 4 months prior to randomization
Previous first-line treatment for intermediate, high, very high risk myelodysplastic syndromes (based on IPSS-R) or CMML with any antineoplastic agents including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitibine and azacitidine. However, previous treatment with hydroxyurea or leukopheresis to reduce WBC count is allowed prior to randomization.
Investigational treatment received within 4 weeks or 5 half-lives of this investigational treatment, whatever is longer, prior to randomization. In case of a checkpoint inhibitor: a minimal interval of 4 months prior to randomization is necessary to allow randomization.
Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3
Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia, primary or secondary myelofibrosis based on WHO 2016 classification (Arber et al 2016)
Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber et al 2016)
History of organ or allogeneic hematopoietic stem cell transplant

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Locations

United States
Yuma Regional Cancer Center
Recruiting
Yuma, 85364
Arizona
United States
Australia
Novartis Investigative Site
Recruiting
Woolloongabba, 4102
Queensland
Australia
Novartis Investigative Site
Recruiting
Clayton, 3168
Victoria
Australia
Novartis Investigative Site
Recruiting
Perth, 6000
Western Australia
Australia
Austria
Novartis Investigative Site
Recruiting
Graz, 8036
-
Austria
Novartis Investigative Site
Recruiting
Innsbruck, A-6020
-
Austria
Novartis Investigative Site
Recruiting
Linz, A-4010
-
Austria
Belgium
Novartis Investigative Site
Recruiting
Brasschaat, 2930
-
Belgium
Novartis Investigative Site
Recruiting
Roeselare, 8800
-
Belgium
Czechia
Novartis Investigative Site
Recruiting
Praha 2, 128 20
Czech Republic
Czechia
Novartis Investigative Site
Recruiting
Brno - Bohunice, 639 01
-
Czechia
Novartis Investigative Site
Recruiting
Praha, 12808
-
Czechia
Finland
Novartis Investigative Site
Recruiting
Helsinki, FIN 00290
-
Finland
Novartis Investigative Site
Recruiting
Kuopio, 70211
-
Finland
France
Novartis Investigative Site
Recruiting
Grenoble, 38043
-
France
Novartis Investigative Site
Recruiting
Lille Cedex, 59037
-
France
Novartis Investigative Site
Recruiting
Paris Cedex 10, 75475
-
France
Novartis Investigative Site
Recruiting
Toulouse, 31059
-
France
Novartis Investigative Site
Recruiting
Tours, 37044
-
France
Novartis Investigative Site
Recruiting
Vandoeuvre Les Nancy, 54511
-
France
Germany
Novartis Investigative Site
Recruiting
Dresden, 01307
Sachsen
Germany
India
Novartis Investigative Site
Recruiting
Ahmedabad, 380009
Gujrat
India
Israel
Novartis Investigative Site
Recruiting
Afula, 1834111
-
Israel
Novartis Investigative Site
Recruiting
Tel Aviv, 6423906
-
Israel
Japan
Novartis Investigative Site
Recruiting
Sapporo, 064 0804
Hokkaido
Japan
Novartis Investigative Site
Recruiting
Isehara, 259-1193
Kanagawa
Japan
Novartis Investigative Site
Recruiting
Osaka Sayama, 589 8511
Osaka
Japan
Novartis Investigative Site
Recruiting
Yamagata, 990 9585
-
Japan
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06351
-
Korea, Republic of
Lithuania
Novartis Investigative Site
Recruiting
Vilnius, LT-08661
-
Lithuania
Singapore
Novartis Investigative Site
Recruiting
Singapore, 119228
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 169608
-
Singapore
Spain
Novartis Investigative Site
Recruiting
Sevilla, 41013
Andalucia
Spain
Novartis Investigative Site
Recruiting
Oviedo, 33006
Asturias
Spain
Novartis Investigative Site
Recruiting
Badalona, 08916
Catalunya
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Valencia, 46010
Comunidad Valenciana
Spain
Novartis Investigative Site
Recruiting
Madrid, 28009
-
Spain
Novartis Investigative Site
Recruiting
Salamanca, 37007
-
Spain
Switzerland
Novartis Investigative Site
Recruiting
Zürich, 8091
-
Switzerland
Taiwan
Novartis Investigative Site
Recruiting
Hualien City, 970
Hualien
Taiwan
Novartis Investigative Site
Recruiting
Liouying Township,
-
Taiwan
Novartis Investigative Site
Recruiting
Taichung, 40447
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 11217
-
Taiwan
Thailand
Novartis Investigative Site
Recruiting
Khon Kaen, 40002
THA
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10330
-
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10400
-
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10700
-
Thailand
Novartis Investigative Site
Recruiting
Chiang Mai, 50200
-
Thailand
Turkey
Novartis Investigative Site
Recruiting
Edirne, 22030
-
Turkey

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

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