What side effects are associated with this type of intervention?

Common treatments for Myelodysplastic Syndrome (MDS) include erythropoiesis-stimulating agents (ESAs), thrombopoietin receptor agonists, hypomethylating agents (HMAs), and lenalidomide. ESAs can increase the risk of thrombosis and require careful monitoring of hypertension. Thrombopoietin receptor agonists, such as romiplostim, may transiently improve platelet counts but have potential risks including increased blast cell counts and progression to acute myeloid leukemia (AML). HMAs like azacitidine and decitabine are associated with cytopenias and other toxicities but generally have a favorable balance of outcomes versus toxicity. Lenalidomide can cause neutropenia, thrombocytopenia, pruritus, rash, and diarrhea, but these side effects are typically manageable.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Myelodysplastic Syndrome (MDS). Hypomethylating agents such as azacitidine and decitabine are commonly used and have shown comparable efficacy and safety profiles. Lenalidomide is another approved drug, particularly effective in patients with del(5q) MDS. Thrombopoietin mimetics like romiplostim have been studied for their potential to improve platelet counts, although their use is controversial due to concerns about increasing the risk of progression to acute myeloid leukemia (AML). These agents represent the primary pharmacological treatments for MDS, focusing on improving blood counts and reducing transfusion needs.

What other types of research exist?

Promising novel alternatives for MDS patients include investigational treatment regimens such as interferon, hydroxychloroquine, BCL6 inhibitors, and smoothened antagonists like LDF225 and BMS-833923. These alternatives are being explored for their potential to eradicate minimal residual disease and offer a functional cure. Additionally, ongoing studies are characterizing the safety, tolerability, and dose for select single agents and combinations in lower-risk MDS patients.

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Corticosteroid

Combination Immunotherapy for Myelodysplastic Syndrome

Phase 1

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

- Thrombocytopenia with platelets <30,000/uL or with clinically significant bleeding or bruising and platelets <50,000/uL

- Neutropenia with an absolute neutrophil count (ANC) <500/ µL or with recurrent and/or severe infections and an ANC that is <1000/ µL and amenable to response assessments by International Working Group (IWG) response criteria in myelodysplasia (Cheson et al 2006)

Must not have

Patients with chronic myelomonocytic leukemia (CMML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

For arms containing canakinumab: Patients with ANC < 500 /µL

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 30 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tested drugs MBG453, NIS793, and canakinumab on patients with lower risk Myelodysplastic Syndromes (MDS). The goal was to see if these drugs could help by boosting the immune system or reducing inflammation.

Who is the study for?

Adults diagnosed with lower risk Myelodysplastic Syndrome (MDS) who have specific symptoms like anemia, low platelets, or neutropenia and are not responding to standard treatments. Participants must be able to undergo bone marrow tests and have a performance status indicating they can still perform daily activities.

What is being tested?

The trial is testing the safety and optimal doses of NIS793, MBG453, and canakinumab alone or in combination for treating MDS. It aims to find out how well patients tolerate these drugs and their combinations.

What are the potential side effects?

Potential side effects may include allergic reactions to the study drugs, increased risk of infections due to immune system suppression by canakinumab, as well as other drug-specific side effects that will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My platelet count is below 30,000/uL, or I have significant bleeding with a count below 50,000/uL.

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My white blood cell count is very low, making me prone to infections.

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I am 18 years old or older.

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I have anemia with low hemoglobin and treatments haven't worked or I can't tolerate them.

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My MDS is classified as very low, low, or intermediate risk with ≤10% bone marrow blasts.

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I can take care of myself but might not be able to do heavy physical work.

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I have anemia with low hemoglobin and haven't used ESA treatments.

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I cannot use standard treatments like lenalidomide due to side effects or other reasons.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with CMML or MDS/MPN.

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My white blood cell count is below 500.

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I haven't had cancer treatment or experimental therapy in the last 14 days or 5 half-lives, whichever is longer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 30 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~30 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 30 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

AE and SAE incidence

Dose intensity

Dose interruption reduction

+1 more

Secondary study objectives

Best Overall Response (BOR) in transfusion dependent and transfusion independent patients

Change from baseline in Absolute Neutrophil Count/White Blood Cells (ANC/WBC) in transfusion dependent and transfusion independent patients

Change from baseline in hemoglobin (Hb) in transfusion dependent and transfusion independent patients

+13 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Arm 5: MBG453 + canakinumab combinationExperimental Treatment2 Interventions

Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.

Group II: Arm 4: MBG453 + NIS793 combinationExperimental Treatment2 Interventions

Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.

Group III: Arm 3: canakinumab single agentExperimental Treatment1 Intervention

Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.

Group IV: Arm 2: NIS793 single agentExperimental Treatment1 Intervention

Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.

Group V: Arm 1: MBG453 single agentExperimental Treatment1 Intervention

Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

NIS793

2021

Completed Phase 3

~880

MBG453

2017

Completed Phase 2

~410

canakinumab

2014

Completed Phase 3

~280

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Myelodysplastic Syndrome (MDS) include hypomethylating agents like azacitidine and decitabine, which work by inhibiting DNA methylation, thereby reactivating tumor suppressor genes and promoting normal cell differentiation. Erythropoiesis-stimulating agents (ESAs) such as epoetin alfa and darbepoetin alfa stimulate red blood cell production, addressing anemia in MDS patients. Thrombopoietin mimetics like romiplostim and eltrombopag aim to increase platelet counts by stimulating the thrombopoietin receptor, although their use is cautious due to potential risks of leukemic transformation. These treatments are crucial as they target specific hematologic deficiencies in MDS, improving patient outcomes and quality of life.

SOHO State of the Art and Next Questions: Management of Myelodysplastic Syndromes With Deletion 5q.Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.