Study of the investigational drug MBG453 in combination with the standard therapy Azacitidine in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML-2)

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Finland, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Lebanon, Lithuania, Malaysia, Mexico, Netherlands, Oman, Portugal, Russian Federation, Saudi Arabia, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States (ICTRP)

ICTRP Studien-ID
NCT04266301 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
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) (BASEC)

Wissenschaftlicher Titel
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) (ICTRP)

Öffentlicher Titel
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) (ICTRP)

Untersuchte Krankheit(en)
Myelodysplastic SyndromesLeukemia, Myelomonocytic, Chronic (ICTRP)

Untersuchte Intervention
Drug: SabatolimabDrug: AzacitidineDrug: Placebo (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator). (ICTRP)

Ein-/Ausschlusskriterien
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

- 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 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 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. (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Overall Survival (ICTRP)

Key secondary endpoint 1: Time to definitive deterioration of fatigue using Functional Assessment of Cancer Therapy (FACIT)-Fatigue score;Key secondary endpoint 2: Red Blood Cell transfusion-free intervals;Key secondary endpoint: Percent of subjects with at least 3 point confirmed improvement from baseline in FACIT-fatigue scoresscore;Key secondary endpoint 4: Percent of subjects with at least 10 point confirmed improvement from baseline in physical functioning using European Or ganization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30);Key secondary endpoint 5: Percent of subjects with at least 10 point confirmed improvement from baseline in emotional functioning using EORTC-QLQ-C30;Percentage of subjects with either CR, or mCR, or PR, or HI in each treatment arm according to International Working Group for MDS (IWG-MDS) as per investigator assessment;Percentage of subjects with SD in each treatment arm according to International Working Group for MDS (IWG-MDS) as per investigator assessment;Progression Free Survival (PFS);Leukemia-free survival;Number of transfusion dependent subjects at baseline who become Red Blood Cells/platelets transfusion independent after randomization;Percentage of transfusion dependent subjects at baseline who become Red Blood Cells/platelets transfusion independent after randomization;Pharmacokinetics of MBG453 (parameter Cmax);Pharmacokinetics of MBG453 (parameter AUC);Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment;Change from baseline in the European Quality of Life (EuroQol) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) score over time;Change from baseline in the European Quality of Life (EuroQoL) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) Visual Analogue Scale over time;Change from baseline to C12D1 of Global Health Status/Quality of Life scores using European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC-QLQ-C30) (ICTRP)

Registrierungsdatum
nicht verfügbar

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Novartis Pharmaceuticals, Novartis Pharmaceuticals (ICTRP)

Sekundäre IDs
2019-002089-11, CMBG453B12301 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04266301 (ICTRP)