Safety and Efficacy of PRG-2302 for Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia Disease.

Inclusion Criteria:

1. Age ≥18 years old, not over 70 years old (including 70 years old);

2. Meet the following diagnostic criteria for recurrent or refractory B-ALL:

A clear diagnosis of B-cell acute lymphoblastic leukemia with any of the following conditions Patients:

• recurrent: recurrence within 12 months after the first remission after standardtreatment;

• refractory:

1.induction No remission after more than 6 weeks of treatment or two courses ofinduction therapy; 2.Two or more CR or CRIs Later recurrence; 3.Relapse for thefirst time after chemotherapy and no remission after at least one salvage treatment; 4.Recurrence after autologous or allogeneic hematopoietic stem cell transplantation;

3. Bone marrow or peripheral blood flow cytometry showed positive CD19 and/or CD22leukemia cells;

4.The proportion of primitive and naive lymphocyte in bone marrow during screeningperiod was ≥ 5%;

5.The functions of important organs are basically normal:

1. Echocardiography indicated cardiac ejection fraction ≥50%, and no obviousabnormality was found in electrocardiogram;

2. Renal function: creatinine clearance (CrCl) (Cockcroft-Gault formula, Appendix

4. ≥30mL/min;

3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0× upperlimit of normal value (ULN);

4. Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP)

• 2.0×ULN (Gilbert syndrome ≤ 3.0×ULN);

5. Blood oxygen saturation >92%;

6. Expected survival≥3 months;

7. ECOG score : 0~2;

8. Willing and signed informed consent.

Exclusion Criteria:

1. Active central nervous system (CNS) leukemia (NCCN guidelines defined as CNS-3grade and CNS-2 patients with neurological symptoms);

2. Subjects with other malignancies within 5 years (except patients who have beencured and have no active disease for more than 3 years prior to screening, andpatients with non-melanoma skin cancer, basal cell or squamous cell skincancer, local prostate cancer, ductal carcinoma in situ, papillary orfollicular thyroid cancer, and carcinoma in situ);

3. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb)positive and peripheral blood hepatitis B virus (HBV) DNA titer greater thanthe normal range; Hepatitis C virus (HCV) antibody positive and peripheralblood HCV RNA titer greater than the normal range; Positive for humanimmunodeficiency virus (HIV) antibodies; Syphilis positive; Peripheral bloodtests positive for cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV);

4. There is an uncontrolled active infection;

5. Patients with clinically significant diseases of the central nervous system,such as epilepsy, cerebrovascular ischemia/bleeding history, cerebellardiseases or other organic brain syndromes or psychosis (except those withprevious central invasion but improved after treatment);

6. Organ failure patients:

7. Heart:a.New York Heart Association (NYHA) Stage III or IV congestive heart failure;b.Had a myocardial infarction or received coronary artery bypass grafting (CABG) or coronary stenting within 6 months or less before signing the ICF; c.Ahistory of clinically significant ventricular arrhythmia, or unexplainedsyncope (other than those due to vasovagal or dehydration); d.History of severenon-ischemic cardiomyopathy;

8. Liver:According to the Wuhan Conference Classification (1983) to reach level III orabove;

9. kidney: Renal insufficiency reaches stage III renal failure or above;

7.Any serious and/or uncontrollable comorbidities that the investigator believes mayinterfere with the assessment during the study;

8.Known allergic reactions, hypersensitivities, intolerances, or contraindicationsto any component of PRG2302 or the drugs that may be used in the study (includingfludarabine, cyclophosphamide, tolumab, albumin), or prior severe allergicreactions;

9.Donor lymphocyte infusion (DLI) was received within 4 weeks prior to anapheresis.

10.Live/attenuated vaccine was administered within 4 weeks prior to anapheresis orduring the planned study period;

11.Major surgery or surgical treatment within 4 weeks for any reason;

12.Patients with a history of allogeneic hematopoietic stem cell transplantation inthe 4 weeks prior to the collection, acute graft-versus-host disease (GvHD) ormoderate-to-severe chronic grade 2 to 4 GvHD in the 4 weeks prior to collection,requiring systemic drug therapy (such as hormones or other immunosuppressants);

13.High doses of chemotherapy within 2 to 4 weeks, intrathecal therapy within 1week, short-acting cytotoxic drugs, TKI and systemic glucocorticoid therapy within 3days, or biologic drugs for disease treatment within 4 weeks;

14.Pregnant women and breastfeeding women cannot stop breastfeeding, and fertile menand their partners or women refuse to use effective contraceptive methods during thestudy period and at the end of the study (1 year after transfusion);In theresearchers' judgment, a patient is fertile: he/she is biologically capable ofhaving children and having a normal sexual life.Female patients who are infertile (i.e. meet at least 1 of the following criteria) : Have undergone hysterectomy orbilateral oophorectomy or bilateral tubal ligation, or have medically confirmedovarian failure, or have medically confirmed postmenopause (at least 12 consecutivemonths of menopause);

15.Patients who cannot collect a sufficient number of mononuclear cells or T cells (e.g., failure to establish a collection pathway, collection failure, or low T cellproportion during screening);

16.Participated in other intervention clinical trials within 3 months;

17.Other medical conditions determined by the investigator to be unsuitable forlymphocyte clearance or cell infusion or other unsuitable participants for studyparticipation.