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No longer recruiting (closed or complete)Last updated: 7 November 2024

STIMULUS-MDS2: This Phase III trial is trying to understand the effect of a new immunotherapy (MBG453) in combination with chemotherapy (azacitidine) compared with azacitidine and a placebo in people with intermediate, high or very high risk myelodysplastic syndrome or chronic myelomonocytic leukaemia-2A Randomized, Double-blind, Placebo-controlled Phase III Multi-center 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)

Trial purpose

Medical clipboardCancer treatment

Tumor type

Blood Cancers Haematological

Age

People18+

Trial acronym

STIMULUS-MDS2

Clinical summary

Summary

This is a randomised trial with experimental and placebo comparator arms. Participants in the Experimental Arm will receive MBG453 plus Azacitidine. A dose of MBG453 800 mg will be administered intravenously (IV) every 4 weeks (Q4W).A dose of Azacitidine 75 mg/m2 will be administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9. Participants in the Placebo Comparator Arm will receive a placebo plus Azacitidine. A dose of Placebo 800 mg will be administered intravenously every 4 weeks (Q4W). A dose of Azacitidine 75 mg/m2 will be administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.

Conditions

This trial is treating people with myelodysplastic syndromes and chronic myelomonocytic leukaemia

Eligibility

Inclusion

  • 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

  • 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.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Novartis Pharmaceuticals

Scientific Title

A Randomized, Double-blind, Placebo-controlled Phase III Multi-center 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)

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