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)

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

In brief

This was a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult participants with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who 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 was to assess clinical effects of MBG453 in combination with azacytidine in adult participants with IPSS-R intermediate, high, very high risk MDS and CMML-2.

Key facts

Study ID: NCT04266301
Run by: Novartis Pharmaceuticals
People needed: 530
Starts: 2020-06-08
Expected to finish: 2024-10-02
Last updated by the study team: 2026-01-13

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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

Where it is running

University of California LA — Los Angeles, California, United States
Yale University School Of Medicine — New Haven, Connecticut, United States
Mayo Clinic Jacksonville — Jacksonville, Florida, United States
University Of Miami — Miami, Florida, United States
Northwestern University — Chicago, Illinois, United States
Massachusetts General Hospital — Boston, Massachusetts, United States
Hackensack University Medical Ctr — Hackensack, New Jersey, United States
Weill Cornell Medicine NY-Presb — New York, New York, United States
University of Rochester Medical Ctr — Rochester, New York, United States
University of Virginia — Charlottesville, Virginia, United States
Novartis Investigative Site — Pilar, Buenos Aires, Argentina
Novartis Investigative Site — Wooloongabba, Queensland, Australia
Novartis Investigative Site — Clayton, Victoria, Australia
Novartis Investigative Site — Perth, Western Australia, Australia
Novartis Investigative Site — Innsbruck, Tyrol, Austria
Novartis Investigative Site — Graz, Austria
Novartis Investigative Site — Linz, Austria
Novartis Investigative Site — Roeselare, West-Vlaanderen, Belgium
Novartis Investigative Site — Brasschaat, Belgium
Novartis Investigative Site — Florianópolis, Santa Catarina, Brazil
Novartis Investigative Site — São Paulo, São Paulo, Brazil
Novartis Investigative Site — São Paulo, São Paulo, Brazil
Novartis Investigative Site — Calgary, Alberta, Canada
Novartis Investigative Site — Toronto, Ontario, Canada
Yuma Regional Cancer Center — Yuma, Arizona, United States

Full record on ClinicalTrials.gov

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