A Study of pCAR-19B in the Treatment of CD19-positive Relapsed/Refractory B-ALL in Children and Adolescents

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

This is a phase II clinical study to evaluate the safety and efficacy of pCAR-19 B cell autologous infusion preparation in the treatment of CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia.

This is a multiple-center, single-arm, open-label study. After meeting the eligibility criteria and enrolling on the trial, patients will undergo leukapheresis for collection of autologous lymphocytes. Once cells have been manufactured, patients will then proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m2 and fludarabine 30mg/m2 for 3 consecutive days followed by the infusion of CD19 CAR T-cells at a target dose of 0.6-2 x106 cells/kg.

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.