SAR443579 for Leukemia

Recruiting at31 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Sanofi

Must not be taking: Antiretrovirals, Corticosteroids

Disqualifiers: Autoimmune disease, Invasive malignancy, HIV, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like high-dose corticosteroids or other investigational drugs when starting the trial.

What makes the drug SAR443579 unique for treating leukemia?

SAR443579 is a novel treatment for leukemia that may offer a unique approach compared to existing therapies, potentially involving a different mechanism of action or targeting specific genetic alterations in leukemia cells. However, specific details about its uniqueness compared to other treatments are not provided in the available research. ^{1 2 3 4 5}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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.

Inclusion Criteria

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

My body weight is at least 10 kg.

I am between 1 and 17 years old.

Exclusion Criteria

I have a genetic condition that affects my bone marrow.

I will use growth factors to prevent blood cell issues during the early trial phase.

Pregnant and breast-feeding women

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

SAR443579 administered intravenously at escalating dose levels to determine the recommended dose for expansion

Up to 6 months

Dose Expansion

SAR443579 administered intravenously at the recommended dose and schedule determined from the dose escalation

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 months

Treatment Details

Interventions

• SAR443579 (BCL-2 inhibitor)

Trial Overview 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).

Participant Groups

Group I: SAR443579 Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

In a study of 4 patients with variant Ph chromosome-positive leukemia, 3 had chronic myeloid leukemia (CML) and 1 had adult B acute lymphoblastic leukemia (B-ALL), with varying cytogenetic abnormalities and responses to treatment.

While all patients responded to treatment with imatinib, the prognosis for the patient with the e13a3 type BCR/ABL fusion gene was poor, leading to relapse and death, whereas the CML patients remained in molecular remission for up to 27 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Characteristics and Prognosis of patients with Variant Philadelphia Chromosome Positive Leukemia]. Zhang, XY., Wu, SX., Guo, XZ., et al.[2018]

A rare case of acute myeloid leukemia (AML) with a specific translocation (t (11;12) (p15;q13)) was identified, which did not respond well to standard treatments like all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), similar to previous cases.

The findings suggest that standard AML treatment regimens may be more effective for this type of leukemia, and hematopoietic stem cell transplantation could be a beneficial option, highlighting the need for further research to explore effective therapies for this rare condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rare Morphology Resembling APL with t (11;12) (p15;q13) in Acute Myeloid Leukemia: Case Report and Literature Review. Hua, J., Bao, X., Xie, Y.[2020]

A patient with acute myeloid leukemia (AML) developed a BCR::ABL alteration after a stem cell transplant, highlighting the genomic complexity of this rare subtype of AML, which is challenging to differentiate from myeloid blast crisis CML.

Functional drug screening suggested that combining ABL1 inhibitors with RAS or PI3K pathway inhibitors could enhance treatment responses, emphasizing the potential for personalized combination therapies based on genomic profiling in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive molecular characterization of a rare case of Philadelphia chromosome-positive acute myeloid leukemia. Rosenberg, MW., Savage, SL., Eide, CA., et al.[2023]

In a study of 994 newly diagnosed acute myeloid leukemia (AML) patients, those with mutations in splicing factor genes (SFmut) had shorter relapse-free survival (RFS) and overall survival (OS) when treated with intensive therapy, but these differences were not significant when patients received venetoclax alongside this therapy.

The presence of SF mutations did not independently worsen outcomes in patients treated with lower-intensity therapy (LI), suggesting that the combination of venetoclax with either treatment type may improve prognostic models for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax abrogates the prognostic impact of splicing factor gene mutations in newly diagnosed acute myeloid leukemia. Senapati, J., Urrutia, S., Loghavi, S., et al.[2023]

In a study of 1023 children with standard-risk acute lymphoblastic leukemia (ALL), 13.6% were identified as having Philadelphia chromosome-like ALL (Ph-like ALL), which is associated with poorer event-free survival rates compared to non-Ph-like ALL (82.4% vs 90.7%).

The study found that 38.8% of Ph-like ALL cases had kinase-activating alterations, but these alterations were less frequent in standard-risk patients compared to high-risk patients, indicating a potential for targeted therapy with kinase inhibitors may be limited in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group. Roberts, KG., Reshmi, SC., Harvey, RC., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical Characteristics and Prognosis of patients with Variant Philadelphia Chromosome Positive Leukemia]. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

A Rare Morphology Resembling APL with t (11;12) (p15;q13) in Acute Myeloid Leukemia: Case Report and Literature Review. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Comprehensive molecular characterization of a rare case of Philadelphia chromosome-positive acute myeloid leukemia. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Venetoclax abrogates the prognostic impact of splicing factor gene mutations in newly diagnosed acute myeloid leukemia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group. [2021]