NCT04266301 · REGISTRY CONDITION SEARCH

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)

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: TERMINATED
Registry last update: 2026-01-13

This was a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult participants with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who are not eligible for intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) according to medical judgment by the investigator. The purpose of the current study was to assess clinical effects of MBG453 in combination with azacytidine in adult participants with IPSS-R intermediate, high, very high risk MDS and CMML-2.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS) (Primary Efficacy Results)

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outcome · POSTED

Overall Survival (OS) (Final Efficacy Results)

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outcome · POSTED

Key Secondary Endpoint 1: Time to Definitive Deterioration of Fatigue Using Functional Assessment of Cancer Therapy (FACIT)-Fatigue Score

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outcome · POSTED

Key Secondary Endpoint 2: Red Blood Cell (RBC) Annualized Transfusion Free Rate for Transfusion

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outcome · POSTED

Key Secondary Endpoint 3: Percentage of Participants With at Least 3 Point Confirmed Improvement From Baseline in FACIT-fatigue Scores

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outcome · POSTED

Key Secondary Endpoint 4: Percentage of Participants With at Least 10 Point Confirmed Improvement From Baseline in Physical Functioning Using European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)

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outcome · POSTED

Key Secondary Endpoint 5: Percentage of Participants With at Least 10 Point Confirmed Improvement From Baseline in Emotional Functioning Using EORTC-QLQ-C30

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outcome · POSTED

Percentage of Participants 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

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outcome · POSTED

Percentage of Participants With Stable Disease (SD) According to International Working Group for MDS (IWG-MDS) as Per Investigator Assessment

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Leukemia-free Survival (LFS)

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outcome · POSTED

Number of Participants Who Become Red Blood Cells (RBC) Transfusion Independent After Randomization

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outcome · POSTED

Number of Participants Who Become Platelets Transfusion Independent After Randomization

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outcome · POSTED

Pharmacokinetics of MBG453 (Parameter Cmax)

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outcome · POSTED

Pharmacokinetics of MBG453 (Parameter AUC)

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outcome · POSTED

ADA Prevalence at Baseline and ADA-positive Participants On-treatment

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outcome · POSTED

Change From Baseline in the European Quality of Life (EuroQol) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) Score Over Time

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outcome · POSTED

Change From Baseline in the European Quality of Life (EuroQoL) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Over Time

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outcome · POSTED

Change From Baseline 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).

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outcome · POSTED

All Collected Deaths

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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 * 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
healthy Volunteers: false
maximum Age: 100 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received sabatolimab plus Azacitidine
intervention Names
Drug: Sabatolimab
Drug: Azacitidine
label
Sabatolimab (MBG453) + Azacitidine
type
EXPERIMENTAL
description
Participants received placebo plus Azacitidine.
intervention Names
Drug: Azacitidine
Drug: Placebo
label
Placebo + Azacitidine
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Sabatolimab (MBG453) + Azacitidine
description
A dose of MBG453 800 mg was administered intravenously (IV) every 4 weeks (Q4W).
name
Sabatolimab
other Names
MBG453
type
DRUG
arm Group Labels
Placebo + Azacitidine
Sabatolimab (MBG453) + Azacitidine
description
A dose of Azacitidine 75 mg/m2 was administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9.
name
Azacitidine
type
DRUG
arm Group Labels
Placebo + Azacitidine
description
A dose of placebo 800 mg was administered intravenously every 4 weeks (Q4W).
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

intervention Model Description

Randomized, double-blind

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 530
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
OS is the time from randomization until death due to any cause.
measure
Overall Survival (OS) (Primary Efficacy Results)
time Frame
up to approx. 39 months
description
OS is the time from randomization until death due to any cause.
measure
Overall Survival (OS) (Final Efficacy Results)
time Frame
up to approx. 52 months

secondary Outcomes

description
FACIT-Fatigue score is a 13-item questionnaire designed to assess fatigue in cancer participants. All items use a 5-point scale ranging from 0 to 4 (0=Not at All to 4=Very Much). The total score ranges from 0 to 52 with higher values representing better quality of life. Time to definitive deterioration of fatigue is defined as time from randomization to at least 3 points worsening from baseline in FACIT-fatigue scores with no subsequently observed improvement above this threshold, or death due to any cause, whichever occurred first.
measure
Key Secondary Endpoint 1: Time to Definitive Deterioration of Fatigue Using Functional Assessment of Cancer Therapy (FACIT)-Fatigue Score
time Frame
up to approx. 52 months
description
Annualized transfusion free rate is defined as the average number of days in RBC transfusion-free intervals in a year (i.e., the total number of days in RBC transfusion-free intervals divided by the total days in the study multiplied by 365.25), where RBC transfusion-free intervals correspond to cumulative times of intervals with no evidence of RBC transfusion for at least 8 weeks at any point after randomization until death due to any cause.
measure
Key Secondary Endpoint 2: Red Blood Cell (RBC) Annualized Transfusion Free Rate for Transfusion
time Frame
up to approx. 52 months
description
FACIT-Fatigue score is a 13-item questionnaire designed to assess fatigue in cancer participants. All items use a 5-point scale ranging from 0 to 4 (0=Not at All to 4=Very Much). The total score ranges from 0 to 52 with higher values representing better quality of life. The responder is defined as having 3 points improvement from baseline confirmed by a second improvement of 3 points at any time, regardless of preceding worsening. A participant who could not improve was considered as a non-responder.
measure
Key Secondary Endpoint 3: Percentage of Participants With at Least 3 Point Confirmed Improvement From Baseline in FACIT-fatigue Scores
time Frame
up to approx. 52 months
description
EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer participants. Participants' responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A high score indicates a high / healthy level of functioning. The responder is defined as having 10 points improvement from baseline confirmed by a second improvement of 10 points at any time, regardless of preceding worsening. A participant who could not improve was considered as a non-responder.
measure
Key Secondary Endpoint 4: Percentage of Participants With at Least 10 Point Confirmed Improvement From Baseline in Physical Functioning Using European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
time Frame
up to approx. 52 months
description
EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer participants. Participants' responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A high score indicates a high / healthy level of functioning. The responder is defined as having 10 points improvement from baseline confirmed by a second improvement of 10 points at any time, regardless of preceding worsening. A participant who could not improve was considered as a non-responder.
measure
Key Secondary Endpoint 5: Percentage of Participants With at Least 10 Point Confirmed Improvement From Baseline in Emotional Functioning Using EORTC-QLQ-C30
time Frame
up to approx. 52 months
description
Response rate of participants with complete remission (CR), or marrow remission (mCR), or partial remission (PR), or hematologic improvement (HI). CR: where the Bone marrow: ≤ 5% blasts with normal maturation of all cell lineages and Peripheral blood: where Hgb ≥ 10 g/dL AND Platelets ≥ 100\*109/L AND Neutrophils ≥ 1.0\*109/L AND Peripheral blasts 0%. mCR: Bone marrow: ≤ 5% blasts and blast count decrease by ≥ 50% compared to baseline; Peripheralblood/transfusion: Marrow CR may be achieved with or without improved blood counts or with or without transfusions PR: All CR criteria except bone marrow: ≥50% decrease from baseline in blasts in bone marrow AND blast count in bone marrow \>5%. HI: restoration or enhancement of the function of the body's blood cell-producing system that must last as least 8 weeks.
measure
Percentage of Participants 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
time Frame
up to approx. 52 months
description
Response rate of participants with stable disease. SD is the failure to achieve at least partial response (PR), but no evidence of progression for \>8 weeks.
measure
Percentage of Participants With Stable Disease (SD) According to International Working Group for MDS (IWG-MDS) as Per Investigator Assessment
time Frame
up to approx. 52 months
description
PFS is defined as the time from randomization to disease progression (including transformation to acute leukemia per WHO 2016), relapse from CR (IWG-MDS), or death. Disease progression: bone marrow blasts increase ≥ 50% over baseline, to \> 5% if initially \< 5%, \> 10% if 5%-\<10%, or \> 20% if 10%-\<20%. Includes a peripheral blood count decrease ≥ 50% from maximum remission/response levels: neutrophils \< 1.0x109/L, platelets \< 100x109/L, or hemoglobin drop ≥ 2 g/dL to \< 10 g/dL, becoming transfusion-dependent. Relapse from CR: baseline bone marrow blast % return, neutrophils decrease ≥ 50% to \< 1.0x109/L, platelets decrease ≥ 50% to \< 100x109/L, or hemoglobin drop ≥ 1.5 g/dL to \< 10 g/dL, becoming transfusion-dependent. Leukemia transformation: \> 20% blasts per WHO 2016 (Arber et al 2016).
measure
Progression Free Survival (PFS)
time Frame
up to approx. 52 months
description
LFS is defined as the time from randomization to ≥ 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or diagnosis of extramedullary acute leukemia, or death due to any cause
measure
Leukemia-free Survival (LFS)
time Frame
up to approx. 52 months
description
Improvement in RBC transfusion independence as per International Working Group for MDS (IWG-MDS) criteria. RBC transfusion independence was defined as having received 0 units of RBC transfusions during at least 8 consecutive weeks after randomization. The number of participants was shown in only those with transfusion dependence at baseline (BL).
measure
Number of Participants Who Become Red Blood Cells (RBC) Transfusion Independent After Randomization
time Frame
up to approx. 52 months
description
Improvement in Platelets transfusion independence as per International Working Group for MDS (IWG-MDS) criteria. Platelets transfusion independence was defined as having received 0 units of Platelets transfusions during at least 8 consecutive weeks after randomization. The number of participants was shown in only those with transfusion dependence at baseline (BL).
measure
Number of Participants Who Become Platelets Transfusion Independent After Randomization
time Frame
up to approx. 52 months
description
Cmax is the maximum (peak) observed drug concentration after single dose administration (mass x volume-1).
measure
Pharmacokinetics of MBG453 (Parameter Cmax)
time Frame
0 hr (pre-dose) & 2 hrs (post-dose) of Cycle (C) 1 Day (D) 8 and 0 hr (pre-dose) & 2 hrs (post-dose) of C3D8

Full study description

brief Summary: This was a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult participants with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who are not eligible for intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) according to medical judgment by the investigator. The purpose of the current study was to assess clinical effects of MBG453 in combination with azacytidine in adult participants with IPSS-R intermediate, high, very high risk MDS and CMML-2.
detailed Description: This was a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult participants with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2). The primary objective of this study was to compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm where OS was the time from randomization until death due to any cause. Participants were randomized in a 1:1 ratio to treatment arms as follow: MBG453 800 mg IV Q4W plus azacitidine, Placebo IV Q4W plus azacitidine. The randomization was stratified into 4 groups: intermediate risk MDS, high risk MDS, very high risk MDS and CMML-2. All participants who discontinued both study treatments were to have entered a long-term post-treatment follow-up including response and PRO assessments, and/or survival follow-up for up to 5 years after the last participant was randomized. Participants were receiving treatment until they experienced progression of disease (including transformation to acute leukemia per WHO 2016 classification), experienced unacceptable toxicity or discontinued the study treatment for other reasons. Continuation of study treatment beyond progression (excluding transformation to acute leukemia: continuation in this case was not possible) could have been possible in selected participants.

Source references

references

citation
Zeidan AM, Giagounidis A, Sekeres MA, Xiao Z, Sanz GF, Hoef MV, Ma F, Hertle S, Santini V. STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Future Oncol. 2023 Mar;19(9):631-642. doi: 10.2217/fon-2022-1237. Epub 2023 Apr 21.
pmid
37083373
type
DERIVED