Using ThisCART19A to treat relapsed B-ALL before stem cell transplant

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Allogeneic Anti CD19 CAR-T Bridging to Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia

This study is testing a new CAR-T therapy called ThisCART19A to see if it can help people with relapsed B cell acute lymphoblastic leukemia feel better before they get a stem cell transplant.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 14 Years to 65 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT05679687 on ClinicalTrials.gov

What this trial studies

This phase 1, open-label study evaluates the safety, efficacy, and pharmacokinetics of ThisCART19A, an allogeneic anti-CD19 CAR-T therapy, in patients with refractory or relapsed B cell acute lymphoblastic leukemia (r/r B-ALL). Participants will undergo lymphodepletion chemotherapy before receiving ThisCART19A infusion, followed by monitoring for 28 days and a two-year follow-up. The study aims to identify the most effective treatment regimen while ensuring a favorable safety profile.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 14 to 65 with relapsed or refractory B-ALL who intend to undergo hematopoietic stem cell transplantation.

Not a fit: Patients who are outside the age range or do not have relapsed or refractory B-ALL may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed or refractory B-ALL, potentially improving survival rates.

How similar studies have performed: Other studies using CAR-T therapies have shown promising results in treating B-ALL, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign a documented IRB-approved ICF prior to any screening procedure.
2. No gender limitation, 14 years ≤ age ≤ 65 years.
3. Intention to HSCT therapy.
4. Meeting the diagnostic criteria of relapsed or refractory B-ALL. Relapsed B-ALL: Reappearance of blasts in the blood or bone marrow (\>5%) or in any extramedullary site after a CR. Refractory B-ALL: Failure to achieve CR or CRi at the end of induction therapy (General refers to a 4-week regimen or a Hyper-CVAD regimen); Subjects with Ph+ disease are eligible if they are intolerant to TKI therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs.
5. Life expectancy ≥ 8 weeks at the time of enrollment.
6. Eastern Cooperative Oncology Group performance status score of 0 or 1.
7. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function:

   1. Adequate marrow function for lymphodepletion chemotherapy assessed by the investigator.
   2. Creatinine clearance \> 30 mL/min according to the Cockcroft-Gault formula;
   3. ALT and AST ≤ 5 × ULN (the upper limit of normal), total bilirubin ≤ 2×ULN. (Subjects with Gilbert syndrome or liver involvement may be included if their total bilirubin is ≤ 3 × ULN.)
   4. Oxygen saturation (SaO2) ≥ 92% on room air.
   5. Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography.
8. CD19-positive leukemia obtained from bone marrow or peripheral blood confirmed by flowcytometry or biopsy during screening.

Exclusion Criteria:

1. Allergic to preconditioning measures.
2. History of allogeneic HSCT.
3. Other malignancies apart from B-cell malignancies within 5 years prior to screening. (Subjects with cured skin squamous carcinoma, basal cell carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be enrolled.)
4. Severe active infection. (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted.)
5. Pulmonary embolism within 3 months prior to enrollment.
6. Severe cardiovascular and cerebrovascular diseases and hereditary diseases intolerant to CAR-T therapy assessed by the investigator prior to enrollment.
7. Presence of symptomatic CNS involvement (both primary and secondary) at screening confirmed by imaging;
8. Active hepatitis B virus (defined as serum HBV-DNA ≥ 2000 IU/mL), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active syphilis infection prior to enrollment. (Subjects with HBV-DNA \< 2000 IU/mL can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.)
9. Vaccinated with influenza vaccine within 2 weeks prior to lymphodepletion chemotherapy. (Subjects vaccinated with SARS-COV19 vaccine or inactivated, live/non-live adjuvant vaccines can be enrolled.)
10. Female subjects who are pregnant, breastfeeding or planning for pregnancy within 1 year after CAR-T cell infusion, or male subjects whose partners are planning for pregnancy within 1 year after CAR-T cell infusion.
11. Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Jia Chen, M.D., Ph.D.

Conditions CAR; Refractory Acute Lymphoblastic Leukemia; Relapsed Adult ALL; Universal CAR-T; allogeneic HCT