Myelodysplastic Syndrome Clinical Trial

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)

Summary

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.

View Full Description

Full 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).

The primary objective of this study is to compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm where OS is the time from randomization until death due to any cause.

Subjects will be randomized in a 1:1 ratio to treatment arms as follow: MBG453 800 mg IV Q4W plus azacytidine, Placebo IV Q4W plus azacitidine The randomization will be stratified into 4 groups: intermediate risk MDS, high risk MDS, very high risk MDS and CMML-2.

All subjects who discontinue both study treatments will enter a long-term post-treatment follow-up including response and PRO assessments, and/or survival follow-up for up to 5 years after the last subject was randomized.

Subjects will be treated until they experience progression of disease (including transformation to acute leukemia per WHO 2016 classification), experience unacceptable toxicity or discontinue the study treatment for other reasons.

Continuation of study treatment beyond progression (excluding transformation to acute leukemia: continuation in this case is not possible) may be possible in selected subjects.

View Eligibility Criteria

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, including persistent monocytosis) by local investigator assessment with WBC < 13 x 109/L at time of initial diagnosis
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 is for people with:

Myelodysplastic Syndrome

Phase:

Phase 3

Estimated Enrollment:

530

Study ID:

NCT04266301

Recruitment Status:

Active, not recruiting

Sponsor:

Novartis Pharmaceuticals

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 146 Locations for this study

See Locations Near You

Yuma Regional Cancer Center
Yuma Arizona, 85364, United States
UCLA Medical Center
Los Angeles California, 90095, United States
Yale University School of Medicine Smilow Cancer Hospital
New Haven Connecticut, 06520, United States
Mayo Clinic Jacksonville
Jacksonville Florida, 32224, United States
University of Miami
Miami Florida, 33136, United States
Northwestern University Div of Hematology/Oncology
Chicago Illinois, 60611, United States
Massachusetts General Hospital
Boston Massachusetts, 02114, United States
Hackensack University Medical Center SC
Hackensack New Jersey, 07601, United States
Weill Cornell Medicine NewYork Presbyterian Hospital
New York New York, 10021, United States
University of Rochester Medical Center Dept.ofUniv.Rochester/JPWilmot
Rochester New York, 14642, United States
University of Virginia University of Virginia
Charlottesville Virginia, 22903, United States
Novartis Investigative Site
Pilar Buenos Aires, B1629, Argentina
Novartis Investigative Site
Woolloongabba Queensland, 4102, Australia
Novartis Investigative Site
Clayton Victoria, 3168, Australia
Novartis Investigative Site
Perth Western Australia, 6000, Australia
Novartis Investigative Site
Graz , 8036, Austria
Novartis Investigative Site
Innsbruck , A-602, Austria
Novartis Investigative Site
Linz , A-401, Austria
Novartis Investigative Site
Brasschaat , 2930, Belgium
Novartis Investigative Site
Roeselare , 8800, Belgium
Novartis Investigative Site
Florianopolis SC, 88034, Brazil
Novartis Investigative Site
Sao Paulo SP, 04014, Brazil
Novartis Investigative Site
Sao Paulo SP, , Brazil
Novartis Investigative Site
Calgary Alberta, T2N 4, Canada
Novartis Investigative Site
Toronto Ontario, M4N 3, Canada
Novartis Investigative Site
Vina del Mar Valparaiso, 25403, Chile
Novartis Investigative Site
Guangzhou Guangdong, 51000, China
Novartis Investigative Site
Guangzhou Guangdong, 51051, China
Novartis Investigative Site
Shenzhen Guangdong, 51803, China
Novartis Investigative Site
Wuhan Hubei, 43002, China
Novartis Investigative Site
Wuhan Hubei, 43003, China
Novartis Investigative Site
Suzhou Jiangsu, 21500, China
Novartis Investigative Site
Chang Chun Jilin, 13002, China
Novartis Investigative Site
Tianjin Tianjin, 30002, China
Novartis Investigative Site
Hangzhou Zhejiang, 31000, China
Novartis Investigative Site
Beijing , 10002, China
Novartis Investigative Site
Beijing , 10073, China
Novartis Investigative Site
Chengdu , 61004, China
Novartis Investigative Site
Jinan , 25001, China
Novartis Investigative Site
Shanghai , 20002, China
Novartis Investigative Site
Shanghai , 20023, China
Novartis Investigative Site
Tianjin , 30005, China
Novartis Investigative Site
Rionegro Antioquia, 05404, Colombia
Novartis Investigative Site
Bogota , 11023, Colombia
Novartis Investigative Site
Praha 2 Czech Republic, 128 2, Czechia
Novartis Investigative Site
Hradec Kralove CZE, 500 0, Czechia
Novartis Investigative Site
Brno - Bohunice , 625 0, Czechia
Novartis Investigative Site
Praha , 12808, Czechia
Novartis Investigative Site
Helsinki , FIN 0, Finland
Novartis Investigative Site
Kuopio , 70211, Finland
Novartis Investigative Site
Grenoble , 38043, France
Novartis Investigative Site
Lille Cedex , 59037, France
Novartis Investigative Site
Paris Cedex 10 , 75475, France
Novartis Investigative Site
Toulouse , 31059, France
Novartis Investigative Site
Tours , 37044, France
Novartis Investigative Site
Vandoeuvre Les Nancy , 54511, France
Novartis Investigative Site
Velbert North Rhine-westphalia, 42551, Germany
Novartis Investigative Site
Dresden Sachsen, 01307, Germany
Novartis Investigative Site
Augsburg , 86179, Germany
Novartis Investigative Site
Duesseldorf , 40479, Germany
Novartis Investigative Site
Frankfurt , 60590, Germany
Novartis Investigative Site
Greifswald , 17475, Germany
Novartis Investigative Site
Jena , 07740, Germany
Novartis Investigative Site
Kiel , 24116, Germany
Novartis Investigative Site
Ulm , 89081, Germany
Novartis Investigative Site
Alexandroupolis Evros, 681 0, Greece
Novartis Investigative Site
Patras , 265 0, Greece
Novartis Investigative Site
Ahmedabad Gujrat, 38000, India
Novartis Investigative Site
Faridabad Haryana, 121 0, India
Novartis Investigative Site
Madurai Tamil NADU, 62510, India
Novartis Investigative Site
Kolkata West Bengal, 70001, India
Novartis Investigative Site
Kolkata West Bengal, 70016, India
Novartis Investigative Site
Delhi , 110 0, India
Novartis Investigative Site
Afula , 18341, Israel
Novartis Investigative Site
Tel Aviv , 64239, Israel
Novartis Investigative Site
Bologna BO, 40138, Italy
Novartis Investigative Site
Catania CT, 95123, Italy
Novartis Investigative Site
Firenze FI, 50134, Italy
Novartis Investigative Site
Genova GE, 16132, Italy
Novartis Investigative Site
Milano MI, 20162, Italy
Novartis Investigative Site
Rozzano MI, 20089, Italy
Novartis Investigative Site
Reggio Calabria RC, 89124, Italy
Novartis Investigative Site
Roma RM, 00133, Italy
Novartis Investigative Site
Nagoya Aichi, 464 8, Japan
Novartis Investigative Site
Kashiwa Chiba, 277 8, Japan
Novartis Investigative Site
Fukuoka city Fukuoka, 812-8, Japan
Novartis Investigative Site
Sapporo Hokkaido, 064 0, Japan
Novartis Investigative Site
Isehara Kanagawa, 259-1, Japan
Novartis Investigative Site
Sendai city Miyagi, 980 8, Japan
Novartis Investigative Site
Nagasaki-city Nagasaki, 852-8, Japan
Novartis Investigative Site
Osaka Sayama Osaka, 589 8, Japan
Novartis Investigative Site
Bunkyo-ku Tokyo, 113-8, Japan
Novartis Investigative Site
Osaka , 545-8, Japan
Novartis Investigative Site
Yamagata , 990 9, Japan
Novartis Investigative Site
Seoul Seocho Gu, 06591, Korea, Republic of
Novartis Investigative Site
Seoul , 03080, Korea, Republic of
Novartis Investigative Site
Seoul , 03722, Korea, Republic of
Novartis Investigative Site
Seoul , 05505, Korea, Republic of
Novartis Investigative Site
Seoul , 06351, Korea, Republic of
Novartis Investigative Site
Beirut , 1107 , Lebanon
Novartis Investigative Site
Vilnius , LT-08, Lithuania
Novartis Investigative Site
Kuching Sarawak, 93586, Malaysia
Novartis Investigative Site
Kuala Lumpur , 59100, Malaysia
Novartis Investigative Site
Pulau Pinang , 10990, Malaysia
Novartis Investigative Site
Selangor , 68000, Malaysia
Novartis Investigative Site
Mexico Distrito Federal, 06726, Mexico
Novartis Investigative Site
Satelite Edo Mexico, 53100, Mexico
Novartis Investigative Site
Morelia Michoacan, 58260, Mexico
Novartis Investigative Site
Estado de Mexico , 52787, Mexico
Novartis Investigative Site
Groningen , 9713 , Netherlands
Novartis Investigative Site
Muscat , 123, Oman
Novartis Investigative Site
Lisboa , 1099 , Portugal
Novartis Investigative Site
Porto , 4200-, Portugal
Novartis Investigative Site
Sain Petersburg , 19702, Russian Federation
Novartis Investigative Site
St Petersburg , 19102, Russian Federation
Novartis Investigative Site
Riyadh , 11211, Saudi Arabia
Novartis Investigative Site
Singapore , 11922, Singapore
Novartis Investigative Site
Singapore , 16960, Singapore
Novartis Investigative Site
Sevilla Andalucia, 41013, Spain
Novartis Investigative Site
Oviedo Asturias, 33011, Spain
Novartis Investigative Site
Salamanca Castilla Y Leon, 37007, Spain
Novartis Investigative Site
Badalona Catalunya, 08916, Spain
Novartis Investigative Site
Barcelona Catalunya, 08035, Spain
Novartis Investigative Site
Valencia Comunidad Valenciana, 46010, Spain
Novartis Investigative Site
Valencia Comunidad Valenciana, 46026, Spain
Novartis Investigative Site
Madrid , 28009, Spain
Novartis Investigative Site
Bern , 3010, Switzerland
Novartis Investigative Site
Zürich , 8091, Switzerland
Novartis Investigative Site
Hualien City Hualien, 970, Taiwan
Novartis Investigative Site
Kaohsiung City , 83301, Taiwan
Novartis Investigative Site
Liouying Township , , Taiwan
Novartis Investigative Site
Taichung , 40447, Taiwan
Novartis Investigative Site
Taipei , 10002, Taiwan
Novartis Investigative Site
Taoyuan , 33305, Taiwan
Novartis Investigative Site
Songkhla Hat Yai, 90110, Thailand
Novartis Investigative Site
Khon Kaen THA, 40002, Thailand
Novartis Investigative Site
Bangkok , 10330, Thailand
Novartis Investigative Site
Bangkok , 10400, Thailand
Novartis Investigative Site
Bangkok , 10700, Thailand
Novartis Investigative Site
Chiang Mai , 50200, Thailand
Novartis Investigative Site
Ankara , 06100, Turkey
Novartis Investigative Site
Edirne , 22030, Turkey
Novartis Investigative Site
Istanbul , 34890, Turkey
Novartis Investigative Site
Izmir , 35040, Turkey
Novartis Investigative Site
Samsun , 55139, Turkey
Novartis Investigative Site
Portsmouth Hants, PO6 3, United Kingdom
Novartis Investigative Site
Edinburgh , EH4 2, United Kingdom
Novartis Investigative Site
Manchester , M20 4, United Kingdom
Novartis Investigative Site
Nottingham , NG5 1, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Myelodysplastic Syndrome

Phase:

Phase 3

Estimated Enrollment:

530

Study ID:

NCT04266301

Recruitment Status:

Active, not recruiting

Sponsor:


Novartis Pharmaceuticals

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.