CD19-targeted CAR T cell therapy for relapsed or refractory B-cell leukemia

A Phase I Open, Single-arm Study of JWCAR029 (CD19-targeted Chimeric Antigen Receptor T Cells) for Patients With Relapsed or Refractory in B-cell Acute Lymphoblastic Leukemia

This study is testing a new CAR T cell therapy for kids and young adults with tough-to-treat B-cell leukemia to see if it's safe and how much of it can be given.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: N/A to 30 Years
• Sex: All
• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd. (Industry-sponsored)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Tianjin, Tianjin)
• Trial ID: NCT05727683 on ClinicalTrials.gov

What this trial studies

This phase I, open-label, single-arm study evaluates the safety and tolerability of JWCAR029, a CD19-targeted CAR T cell therapy, in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). The study employs a 3+3 dose exploration design to determine the recommended phase II dose and/or maximum tolerated dose based on dose limiting toxicity (DLT) assessments conducted within 28 days post-infusion. Enrollment will begin at the lowest dose level, with subsequent cohorts receiving higher doses based on safety and antitumor activity outcomes.

Who should consider this trial

Good fit: Ideal candidates are pediatric and young adult patients aged 30 years or younger with relapsed or refractory B-ALL.

Not a fit: Patients with other types of leukemia or those who do not meet the specific eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for young patients with difficult-to-treat B-ALL.

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

Eligibility criteria

Inclusion Criteria:

1. Age ≤ 30 years and weight ≥10kg.
2. Patients with r/r B-ALL, defined as morphological disease in the bone marrow(≥5% blasts) and either of the following:

   * ≥2 BM relapse;
   * Refractory defined as relapse if first remission\<12 months or not achieving a CR after 1 cycle of a standard induction chemotherapy regimen for relapsed leukemia;primary chemo-refractory as defined by not achieving a CR after 1 cycle of a conventional chemotherapy or 2 cycles of a standard induction chemotherapy regimen for relapsed leukemia;
   * Any BM relapse after HSCT which must be ≥90 days from HSCT at the time of screening, and be required free from GVHD and ended from any immunosuppressive therapy ≥1 month at the time of screening;
   * Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI therapy, or if TKI therapy is contraindicated.

   Note: Patients with MRD+ after bridging therapy will be allowed for treatment.
3. Karnofsky (age ≥16 years) or Lansky (age \<16 years) performance status \>60.
4. Adequate organ function.
5. Vascular access is sufficient for leukocyte isolation.
6. Expected survival time \> 3 months.
7. Any non-hematological toxicity due to previous treatment, except for alopecia and peripheral neuropathy, must be restored to ≤ grade 1.
8. Females of childbearing potential (all female subjects who are physiologically capable of becoming pregnant) must agree to use a highly effective method of contraception for 1 year following JWCAR029 infusion; male subjects whose partners are of childbearing potential must agree to use an effective barrier method of contraception for 1 year following JWCAR029 infusion.

Exclusion Criteria:

1. leukemic CNS involvement with active CNS lesions and significant neurodegenerative manifestations, or subjects with CNS grade CNS-2/CNS-3 as assessed by NCCN guidelines (subjects rated CNS-2 due to puncture injury may be enrolled).
2. existing or previous clinically significant CNS lesions such as epilepsy, epileptic seizures, paralysis, aphasia, cerebral edema, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, etc.
3. Patients with genetic syndromes other than Down syndrome.
4. Patients with Burkitt's lymphoma.
5. History of malignancy other than B-ALL for at least 2 years prior to enrollment.
6. Subject has HBV, HCV, HIV or syphilis infection at the time of screening.
7. Subject has deep vein thrombosis (DVT) (cancer thrombosis or thrombosis) or pulmonary artery embolism (PE) or is on anticoagulation therapy for DVT or PE within 3 months prior to signing the informed consent form
8. uncontrolled systemic fungal, bacterial, viral or other infections.
9. Combination of active autoimmune diseases requiring immunosuppressive therapy.
10. Acute or chronic graft-versus-host disease.
11. History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart disease.
12. Women who are pregnant or lactating. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to initiation of lymphocyte clearance chemotherapy.
13. Previous treatment with CAR-T cells or other gene-modified T cells.
14. Previous anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
15. Relevant medications or treatments within a specified time frame.
16. The presence of any factors affecting the subject's compliance with the protocol, including uncontrollable medical, psychological, family, sociological, or geographic conditions, as determined by the investigator; or unwillingness or inability to comply with the procedures required in the study protocol.
17. Known life-threatening allergic reactions, hypersensitivity reactions, or intolerance to JWCAR029 cell formulation or its excipients.

Where this trial is running

Tianjin, Tianjin

• Hematology Hospital, Chinese Academy of Medical Sciences — Tianjin, Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Xiaofan Zhu, PhD — Hematology Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Xiaofan Zhu, PhD

Conditions Acute Lymphocytic Leukemia; JWCAR029; Relapsed/Refractory; Pediatric and young adults