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

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

This is a phase I clinical study to evaluate the safety and tolerability of pCAR-19B in patients with relapsed or refractory B-ALL, and to obtain the maximum tolerated dose of pCAR-19B and phase II Recommended dose.

This is a single-center, single-arm, open-label study. The study plans to set up 3 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 9-18 subjects with relapsed or refractory B-ALL.pCAR-19B will be infused to the subject by intravenous infusion.

Inclusion Criteria:

1. Diagnosed with B-ALL，and meet one of the following conditions:

   1. First-line or multiple-line salvage chemotherapy did not achieve complete remission；
   2. Early relapse after complete remission (<12 months), or late relapse after complete remission (≥12 months) and complete remission has not been achieved after 1 course of treatment；
   3. Relapse after autologous or allogeneic hematopoietic stem cell transplantation;

2. Ph+ALL patients should also receive at least two TKI treatments；

3. For allogeneic hematopoietic stem cell transplant subjects, the following conditions must be met：

   1. Allo-HSCT takes ≥6 months before pCAR-19B infusion；
   2. No GVHD of grade 2 or above occurred within 2 weeks before PBMC collection;

4. Express CD19;

5. 3~21 years old, no gender limit;

6. The expected survival time is more than 12 weeks;

7. KPS>60;

8. No serious mental disorders;

9. The function of important organs is basically normal:

   1. Heart function: echocardiography indicates that the cardiac ejection fraction is ≥50%, and the electrocardiogram has no obvious abnormalities;
   2. Renal function: serum creatinine≤2.0×ULN;
   3. Liver function: ALT and AST ≤5×ULN;
   4. Total bilirubin and alkaline phosphatase≤3×ULN ;
   5. Blood oxygen saturation>92%.

10. Have standards for apheresis or venous blood collection, and no other cell collection contraindications;

11. The patient himself or his guardian agrees to participate in the clinical trial and signs the ICF, indicating that he understands the purpose and procedures of the clinical trial and is willing to participate in the research.

Exclusion Criteria:

1. With central nervous system disease at the time of screening;

2. Have received CAR-T therapy or other genetically modified cell therapy;

3. Participated in other clinical studies within 1 month before screening;

4. Have received the following anti-tumor treatments before screening: received chemotherapy, targeted therapy or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter);

5. Have received a live attenuated vaccine within 4 weeks before screening;

6. Cerebrovascular accident or seizure occurred within 6 months before signing the ICF;

7. Suffered from any of the following heart diseases:

   1. NYHA stage III or IV congestive heart failure;
   2. Myocardial infarction or CABG occurred ≤6 months before enrollment;
   3. Clinically significant ventricular arrhythmia, or history of unexplained syncope (except for cases caused by vasovagal or dehydration);
   4. History of severe non-ischemic cardiomyopathy.

8. Uncontrollable infection in the 2 weeks before screening；

9. Active autoimmune diseases；

10. 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；

11. HBsAg or HBcAb positive and HBV DNA is greater than the normal range; HCV antibody is positive and HCV RNA greater than the normal range; HIV antibody positive; syphilis positive; CMV DNA positive;

12. 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;

13. Other situations considered by the researcher to be unsuitable to participate in the study.