bone marrow disorder myelodysplasia
Conditions
Interventions
Treatment with azacitidine and MBG453/placebo
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion 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 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) Or Morphologically confirmed diagnosis of Chronic Myelomonocytic Leukemia -2 based on WHO 2016 classification (Arber et al 2016)(persistant PB monocytosis >= 1 x109/L and monocytes accounting for >= 10% of the WBC differential count) by local investigator assessment • 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 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 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 Please refer to protocol for further details and any additional inclusion criteria.
Exclusion criteria
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-2 with any antineoplastic agents including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or 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 grade 2 or higher based on WHO 2016 classification (Arber et al 2016). Patients with myelofibrosis grade 1 must not be enrolled if they have symptoms of concurrent myeloproliferative neoplasm • Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber et al 2016) • History of organ or allogeneic hematopoietic stem cell transplant Please refer to protocol for further details and any additional exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary objectives • To compare time to definitive deterioration of fatigue in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm as measured by FACIT-Fatigue • To compare RBC transfusion-free intervals in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm • To compare improvement of fatigue in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm using FACIT-Fatigue • To compare improvement of physical functioning in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm using EORTC QLQ-C30 • To compare improvement of emotional functioning in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm using EORTC QLQ-C30 | — |
Countries
Netherlands
Outcome results
None listed