Azacitidine + MBG453/placebo in patients with MDS or CMML-2

• Research type

  Research Study

• Full title

  A randomised, double-blind, placebo-controlled phase III multi-centre 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)

• IRAS ID

  269626

• Contact name

  Pierre Zimmermann

• Contact email

  pierre.zimmermann@novartis.com

• Sponsor organisation

  Novartis Pharma AG

• Eudract number

  2019-002089-11

• Clinicaltrials.gov Identifier

  NCT04266301

• Duration of Study in the UK

  7 years, 2 months, 5 days

• Research summary

  It is estimated that 15,000 to 20,000 new cases of Myelodysplastic Syndromes (MDS) are diagnosed annually in the USA (Klepin 2016). In Europe, the incidence rate of MDS is about 2 new cases per 100,000 each year (Visser et al 2012). The incidence of MDS is more frequent in male patients and increases with age, with a median age at diagnosis of about 70 years.

  Current treatment guidelines for MDS recommend modification of the disease with
  hematopoietic stem cell transplantation (HSCT, treatment with a curative intent), intensivechemotherapy or hypomethylating agents (HMAs; azacitidine and decitabine.

  Prognosis is poor and life expectancy is short with higher risk (intermediate, high, or very high) MDS, and Chronic Myelomonocytic Leukemia 2 (CMML-2) patients treated with the current standard of care based on hypomethylating agents. HMAs represent the standard of care for the vast majority of patients who cannot receive HSCT or cannot be treated with intensive chemotherapy. In MDS patients without
  major co-morbidities who are classified as higher risk, and who do not qualify for
  transplantation or intensive chemotherapy, HMAs are the first-line reference
  treatment. Azacitidine is the sole HMA which showed a prolongation of overall survival (OS) compared to conventional care regimens among patients with higher risk MDS.

  The anti-TIM-3 monoclonal antibody MBG453 is a novel immunotherapeutic agent with
  promising activity seen in AML and higher risk MDS. The purpose of the current study is to assess clinical effects of MBG453 in combination with azacitidine in adult subjects with higher risk MDS and CMML-2. This study will compare MBG453 plus azacitidine or placebo plus azacitidine.

  It is planned that the study will run at 5 sites in the UK, recruiting a total of 10 patients.

  Lay summary of study results: The English lay summary will be available one year post global LPLV (02/10/2025). It will be available to PIs to share with patients and posted in the public domain on Novartis public website https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.novctrd.com%2F&data=05%7C02%7Ccoventryandwarwick.rec%40hra.nhs.uk%7C6c95f05a0ee74fdbc7a708de3c8f627c%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639014783703140219%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=6x%2BHosZ7TjBkfj2bM3OpIy2MVowm20TOXYjrCEoG%2FgQ%3D&reserved=0
  

• REC name

  West Midlands - Coventry & Warwickshire Research Ethics Committee

• REC reference

  20/WM/0181

• Date of REC Opinion

  5 Aug 2020

• REC opinion

  Further Information Favourable Opinion