Treatment of relapsed or refractory B-ALL in children and adolescents using pCAR-19B

A Phase II Clinical Study of Anti-CD19 CAR-T Therapy (pCAR-19B) in the Treatment of CD19-positive Relapsed/Refractory B-ALL

This study is testing a new CAR T-cell therapy called pCAR-19B to see if it can help children and teens with hard-to-treat B-cell leukemia feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 3 Years to 21 Years
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: CAR-T, chemotherapy, CAR T, cyclophosphamide, fludarabine
• Locations: 10 sites (Beijing, Beijing Municipality and 9 other locations)
• Trial ID: NCT05334823 on ClinicalTrials.gov

What this trial studies

This phase II clinical study evaluates the safety and efficacy of pCAR-19B, an autologous CAR T-cell therapy, for treating CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in children and adolescents. Participants will undergo leukapheresis to collect their lymphocytes, which will then be modified to express the CAR targeting CD19. Following cell manufacturing, patients will receive lymphodepleting chemotherapy before the infusion of the modified T-cells. The study is conducted at multiple centers and aims to provide a new treatment option for this challenging condition.

Who should consider this trial

Good fit: Ideal candidates include children and adolescents diagnosed with CD19-positive relapsed or refractory B-ALL who have not responded to standard treatments.

Not a fit: Patients with other types of leukemia or those who are not CD19-positive may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could offer a new hope for children and adolescents with relapsed or refractory B-ALL, potentially leading to improved remission rates.

How similar studies have performed: Other studies using CAR T-cell therapies for B-ALL have shown promising results, indicating that this approach has potential based on previous successes.

Eligibility criteria

Inclusion Criteria:

1. The patient himself or his guardian agrees to participate in this clinical trial and signs the Informed Consent Form (ICF), indicating that he understands the purpose and procedures of this clinical trial and is willing to participate in the research;
2. Diagnosed with B-ALL，and meet one of the following conditions:

   1. Refractory B-ALL: early-stage refractory patients who failed to achieve complete remission after 2 courses of standard induction chemotherapy;
   2. Relapsed B-ALL: patients with early relapse (\<12 months) after complete remission;or late relapse (≥12 months) after complete remission, and relapsed patients who have not achieved complete remission after standard treatment or have poor response to early treatment; experience Patients with 2 or more bone marrow recurrences; patients with recurrence after allogeneic hematopoietic stem cell transplantation;
   3. For Ph+ALL patients, patients who have not achieved complete remission after receiving at least two Tyrosine kinase inhibitors (TKI) treatments or have relapsed after complete remission (except those who cannot tolerate TKI treatment or have contraindications to TKI treatment or have T315i mutation resistance to TKI drugs);
3. The malignant cells in the bone marrow were confirmed to express CD19 by flow cytometry;
4. Bone marrow morphology at the time of screening indicated that blasts≥ 5%;
5. Eastern Cooperative Oncology Group (ECOG) 0-1 points ;
6. Expected survival is ≥ 12 weeks;
7. The function of important organs is basically normal:

   1. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
   2. Renal function: serum creatinine≤2.0×ULN;
   3. Liver function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤5.0×ULN;
   4. Total bilirubin≤2.0×ULN (for Gilbert syndrome, total bilirubin≤3.0×ULN);
   5. Blood oxygen saturation≥92% in non-oxygen state.
8. No serious mental disorder;
9. Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;
10. Subjects of childbearing age agree to use reliable and effective contraceptive methods for contraception (excluding rhythm contraception) from signing the informed consent to receiving pCAR-19B cell infusion within 1 year.

Exclusion Criteria:

1. Relapse of isolated extramedullary disease;
2. Active central nervous system leukemia at screening, defined as Central Nervous System (CNS)-grade 2 and 3 according to National Comprehensive Cancer Network (NCCN) guidelines (note: those with central nervous system involvement but improved after treatment can be included);
3. Those who have received CAR-T therapy or other gene-modified cell therapy before screening;
4. Received anti-CD19 drug treatment before screening;
5. Received the following anti-tumor treatments before screening: Received chemotherapy, targeted therapy and other drug treatments within 14 days or at least 5 half-lives (whichever is shorter); Received radiotherapy within 14 days;
6. HBsAg or HBcAb positive and hepatitis B virus (HBV) DNA is greater than the normal range; hepatitis C virus (HCV) antibody is positive and HCV RNA greater than the normal range; HIV antibody positive; syphilis positive; Cytomegalovirus (CMV) DNA positive;
7. Have any of the following heart conditions:

   1. New York Heart Association (NYHA) stage III or IV congestive heart failure;
   2. Myocardial infarction or coronary artery bypass grafting within 6 months prior to enrollment (CABG);
   3. Clinically significant ventricular arrhythmia, or history of syncope of unknown origin (by vasovagal except those caused by menstruation or dehydration);
   4. History of severe non-ischemic cardiomyopathy;
8. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening;
9. The presence of grade 2-4 acute graft-versus-host disease (GVHD) or moderate to severe chronic GVHD within 4 weeks before screening;
10. Cerebrovascular accident or epileptic seizure within 6 months before screening;
11. Active autoimmune diseases；
12. Patients with malignant tumors other than acute lymphoblastic leukemia within 5 years before screening, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection, and duct in situ after radical resection cancer;
13. Received live attenuated vaccine within 4 weeks before screening;
14. Participated in other interventional clinical studies before screening, including: the last use of unmarketed new drugs is less than 3 months from the time of cell reinfusion, or the last use of marketed drugs is less than 5 half-lives from the time of cell reinfusion;
15. Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving pCAR-19B cell reinfusion;
16. Other investigators deem it inappropriate to participate in the study.

Where this trial is running

Beijing, Beijing Municipality and 9 other locations

• Beijing Children's Hospital.Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)
• Beijing GoBroad Boren Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Pediatric Hematology department of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Xiehe Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• The Second Xiangya Hospital, Central South University — Changsha, Hunan, China (Recruiting)
• Children's Hospital Of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• The First Affiliated Hospital Of Nanchang University — Nanchang, Jiangxi, China (Recruiting)
• West China Second University Hospital,Sichuan University — Chengdu, Sichuan, China (Recruiting)
• Institute Of Hematology&Blood Diseases Hospital,Chinese Academy Of Medicai Sciences — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Tianyou Wang, M.D. Ph.D — Beijing Children's Hospital
• Study coordinator: Tianyou Wang, M.D

Conditions Acute Lymphoblastic Leukemia; Relapsed Pediatric ALL; Refractory Acute Lymphoblastic Leukemia; CAR-T; CD19; B-ALL