CD19-targeted mRNA therapy delivered by lipid nanoparticles for B-cell blood cancers

Exploratory Study on mRNA Therapeutic Drug Targeting CD19 for the Treatment of Hematologic Malignancies

It will try a lipid-nanoparticle mRNA therapy that generates CD19-targeted CAR-T activity inside the body for adults (18–70) with relapsed or refractory CD19-positive B-cell leukemia or lymphoma who have no standard treatment options.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 47 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Xinqiao Hospital of Chongqing (Academic / other)
• Drugs / interventions: chimeric antigen receptor
• Locations: 1 site (Chongqing, Chongqing Municipality)
• Trial ID: NCT07349849 on ClinicalTrials.gov

What this trial studies

This early Phase 1 interventional trial will administer an in vivo CAR-T drug formulated as lipid nanoparticle (LNP) mRNA encoding a CD19-targeting construct to adult patients with CD19-positive B-cell malignancies. The LNPs protect the mRNA and promote intracellular delivery so the patient's own T cells can translate the CAR construct without ex vivo cell manufacturing. As an early-phase trial the primary focus is on safety, tolerability, and initial dosing, with close monitoring for immune-related toxicities and any anti-tumor activity. The single-center study is conducted at Xinqiao Hospital in Chongqing and enrolls adults with adequate organ function and ECOG performance status 0–1 who meet the listed inclusion and exclusion criteria.

Who should consider this trial

Good fit: Adults aged 18–70 with confirmed CD19-positive B-cell lymphoma or lymphocytic leukemia, expected survival over 12 weeks, ECOG 0–1, measurable disease where required, and no guideline-recommended standard treatment options are the intended candidates.

Not a fit: Patients who previously received CAR-T or other transgenic T-cell therapies, have uncontrolled HIV/HBV/HCV infection, CNS lymphoma or brain metastases, other uncontrolled malignancies, or poor performance status are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this could provide a less complex, non-viral way to generate CD19-directed CAR-T activity and offer a treatment option for patients without standard therapies.

How similar studies have performed: mRNA LNP technology has proven successful for vaccines and ex vivo CD19 CAR-T therapies are effective, but in vivo LNP-mediated CAR-T for CD19 is largely novel and unproven in humans.

Eligibility criteria

Inclusion Criteria:

* 1\. Age range of 18-70 years old, gender not limited;
* 2\. Expected survival time exceeds 12 weeks;
* 3\. B-cell lymphoma or lymphocytic leukemia diagnosed with CD19+, with no standard treatment options recommended according to guidelines
* 4\. There are assessable lesions (applicable only to lymphoma patients);
* 5\. The physical fitness status score of the Eastern Cancer Collaboration Group (ECOG) is 0 or 1;
* May involve other inclusion criteria

Exclusion Criteria:

* 1\. Accompanied by other uncontrolled malignant tumors;
* 2\. Previously received chimeric antigen receptor therapy or other transgenic T cell therapy;
* 3\. Known history of HIV or hepatitis B (HBsAg positive and HBV DNA reaching the detection limit) or hepatitis C virus (anti HCV positive) infection;
* 4\. Participants with a history of CNS lymphoma, malignant cells in cerebrospinal fluid, or brain metastases;
* 5\. The researcher believes that there are any other factors that are not suitable for the study participants to enter this trial.

May involve other exclusion criteria

Where this trial is running

Chongqing, Chongqing Municipality

• Department of Hematology, Xinqiao Hospital — Chongqing, Chongqing Municipality, China (Recruiting)

Conditions B-cell Malignancies