MDS, CMML-2
Conditions
Interventions
Active agent arm: MBG453 800 mg Q4W i.v. plus Aza 75 mg/m2 i.v. or s.c.
Pracebo arm: Placebo 800 mg Q4W i.v. plus Aza 75 mg/m2 i.v. or s.c.
Sponsors
Novartis Pharma. K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study 2. Age >= 18 years at the date of signing the informed consent form (ICF) 3. Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on WHO 2016 classification by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R) as per Greenberg et al 2012: -Very high (> 6 points) -High (> 4.5 - = 3 - == 30 mL/min/1.73m2 (estimation based on Modification of Diet in Renal Disease (MDRD) formula, by local laboratory) 9. AST and ALT =< 3 x upper limit of normal (ULN) 10. Total bilirubin =< 1.5 x ULN (except in the setting of isolated Gilbert syndrome, where subjects may only be included with direct bilirubin =< 1.5 x ULN) 11. Subject is able to communicate with the investigator, and has the ability to comply with the requirements of the study procedures
Exclusion criteria
Exclusion criteria: 1. 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. 2. 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 decitabine or azacitidine. However, previous treatment with hydroxyurea or leukapheresis to reduce WBC count is allowed prior to randomization. 3. 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. 4. Current use or use 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. 5. Live vaccine administered within 30 days prior to randomization. 6. History of severe hypersensitivity reaction to any ingredients of the study treatments (azacitidine or MBG453) or their excipients, or to monoclonal antibodies. 7. Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification with revised International Prognostic Scoring System (IPSS-R) 470 ms at screening. Subjects with active infection requiring parenteral antibacterial, antiviral or antifungal therapy which are controlled by adequate treatment are eligible. 15. Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Subjects whose disease is controlled under antiviral therapy should not be excluded. 16. HIV infection not controlled by standard therapy and/or with known history of opportunistic infection. 17. Any other co-morbi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy To compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm | — |
Countries
Asia except Japan, Europe, Japan, North America, South America
Contacts
Public ContactKyosuke Yamauchi
Novartis Pharma. K.K.
Outcome results
None listed