What side effects are associated with this type of intervention?

Common treatments for Myelodysplastic Syndrome (MDS) include azacitidine and decitabine, which are hypomethylating agents. The most frequent side effects of these treatments are hematologic toxicities such as neutropenia, anemia, and thrombocytopenia. Gastrointestinal issues, including nausea, vomiting, and diarrhea, are also common. Additionally, patients may experience fatigue, injection site reactions, and increased risk of infections. These side effects are similar to those observed in treatments with anti-leukemic activity, such as those being studied in the SAR443579 trial.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Myelodysplastic Syndrome (MDS) with anti-leukemic activity. Hypomethylating agents such as azacitidine and decitabine are commonly used and have shown efficacy in treating MDS. Azacitidine is approved for the treatment of MDS that has progressed from myelodysplastic syndromes, while decitabine is approved by the EMA for AML but not by the FDA for MDS. Additionally, the combination of decitabine with cedazuridine, an oral formulation, is approved for MDS. These treatments aim to improve blood counts and reduce the risk of progression to acute myeloid leukemia (AML).

What other types of research exist?

Promising novel alternatives to SAR443579 for Myelodysplastic Syndrome (MDS) patients include: 1) Venetoclax combined with Azacitidine, which has shown efficacy in AML patients with IDH1/2 mutations and could be relevant for MDS. 2) Fedratinib, particularly for patients previously treated with ruxolitinib, as it has shown benefit in myelofibrosis, a related condition. 3) Imetelstat, a telomerase inhibitor, which is being investigated in clinical trials for myelofibrosis and may have potential for MDS.

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BCL-2 inhibitor

SAR443579 for Leukemia

Phase 1 & 2

Recruiting

Research Sponsored by Sanofi

Eligibility Criteria Checklist

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

Must have

Confirmed diagnosis of CD123 + HR-MDS with IPSS-R risk category of intermediate or higher

Body weight at least 10 kg

Must not have

Known inherited bone marrow failure syndromes for pediatric arm participants

Radiotherapy during the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called SAR443579 to see if it is safe and effective for treating blood cancers. The study will look at how the drug moves through and affects the body, and whether it can help fight cancer. Patients with various types of blood cancers are participating in this study.

Who is the study for?

This trial is for children and adults with certain blood cancers like AML, B-ALL, HR-MDS, or BPDCN that have come back or didn't respond to treatment. Participants must be at least 12 years old, weigh over 40 kg, and not have any treatments left that could help them. They can't join if they've had specific prior therapies like CAR-T or anti-CD123 agents, active infections including HIV/AIDS or hepatitis B/C, severe heart issues, poor physical condition (ECOG >2), autoimmune diseases needing strong medication, other active cancers requiring treatment (except some skin cancers), are pregnant/breastfeeding or legally institutionalized.

What is being tested?

The study tests SAR443579 infusion's safety and effectiveness against various blood-related cancers in a Phase 1/Phase 2 trial. It involves gradually increasing the dose to find the safest amount that works best (dose escalation) and then giving it to more people at this dose level (dose expansion).

What are the potential side effects?

While specific side effects of SAR443579 aren't listed here due to its novel status as a first-in-human study drug; generally such drugs may cause immune system reactions leading to inflammation in different body parts, potential organ damage depending on where the reaction occurs along with common chemotherapy-associated risks like fatigue, nausea and increased infection risk.

Eligibility Criteria

Inclusion Criteria

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

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My condition is HR-MDS with intermediate or higher risk.

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My body weight is at least 10 kg.

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I am between 1 and 17 years old.

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I have been diagnosed with AML, but not APL or JMML.

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My leukemia is CD123 positive without cancer outside the bone marrow.

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I am at least 1 year old or my child is, and I can sign the consent form.

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I am 12 years old or older.

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I have been diagnosed with BPDCN as per the latest WHO guidelines.

Exclusion Criteria

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

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I have a genetic condition that affects my bone marrow.

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I will be receiving radiotherapy during the study.

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My heart doesn't pump blood well.

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My leukemia has spread to my brain or spinal cord.

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I have had a solid organ transplant.

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I am taking more than 10 mg/day of corticosteroids at the start of the trial.

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I need help with my daily activities due to my health condition.

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I do not have AIDS, HIV, active hepatitis B or C, or COVID-19.

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I am under 16 and mostly need help with daily activities.

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I am currently on or recently needed strong medication for an autoimmune disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 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

Escalation Part: Incidence of dose-limiting toxicity (DLT)

Expansion/Optimization part (Cohort B), MDS: Overall response rate (CR + CR equivalent + PR + CRL + CRh + HI) according to the IWG 2023 MDS response criteria

Expansion/Optimization part (Cohorts A1, A2 & D), AML: Proportion of participants who have a CR + CRh + CRi according to the modified AML IWG 2003 criteria

+1 more

Secondary study objectives

Escalation and Expansion/Optimization parts - Cohorts A, B, C and D: Ctrough

Escalation and Expansion/Optimization parts - Cohorts A, B, C and D: Incidence of ADA

Escalation and Expansion/Optimization parts - Cohorts A, B, C and D: Number of participants with TEAEs

+23 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: SAR443579Experimental Treatment1 Intervention

Dose Escalation: SAR443579 administered intravenously at escalating dose levels. Dose Expansion: SAR443579 administered intravenously at the recommended dose and schedule determined from the dose escalation.

0 / 18Eligibility 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

The most common treatments for Myelodysplastic Syndrome (MDS) include hypomethylating agents such as azacitidine and decitabine. These agents work by inhibiting DNA methyltransferase, leading to hypomethylation of DNA and reactivation of tumor suppressor genes, which can induce cell differentiation and apoptosis in malignant cells. This is crucial for MDS patients as it can reduce the progression of the disease and improve survival rates. Additionally, treatments like venetoclax, a BCL2 inhibitor, are used in combination with hypomethylating agents to enhance anti-leukemic activity by promoting apoptosis in cancer cells. These mechanisms are vital as they target the underlying pathophysiology of MDS, offering potential for better disease management and improved patient outcomes.

SOHO State of the Art and Next Questions: Management of Myelodysplastic Syndromes With Deletion 5q.Combination therapy with DNA methyltransferase inhibitors in hematologic malignancies.