Evaluate the Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With R/R B-ALL

Korábbi kezelés

• Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma,basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.
• Patients had pulmonary embolism within 3 months prior to enrollment.
• Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment.
• Combined systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. Or systemic diseases that require long-term use of immunization Inhibitor.
• Vaccinated with influenza vaccine within 2 weeks prior to cleansing (SARS-COV19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) .
• Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.

Más betegség

• Allergic to preconditioning measures.
• Uncontrollable bacterial, fungal and viral infection during screening.
• Active HBV or HCV or HIV or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenufovir, etc, and supervisory the relative indication during the treatment.
• Any ineligibility conditions considered by the investigator that may increase the risk of the subject or interfere with the results of the study;

Egyéb

• Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening.
• Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

• All subjects or legal representatives must sign a voluntary letter of consent approved by the IRB in person prior to the commencement of any screening procedure;
• Patients diagnosed with B-ALL according to the Chinese Guidelines for the Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2021 edition);
• There is no gender limitation, age 18-70(upper limit not included);
• Consistent with the diagnosis of recurrent refractory B-ALL. Recurrence： was defined as the recurrence of lymphoblasts（≥5%） in peripheral blood or bone marrow or extramedullary diseasefor patients who had acquired CR ; Refractory ：was defined as failure to CR or CRi at the end of induction therapy (generally referred to 4-week regimen or Hyper-CVAD regimen);Patients with Ph+ R/R ALL who failed after 2-line TKI treatment, were intolerant to TKI treatment or were not suitable for TKI treatment;
  • The following factors can coexist:
  • Failure to prepare autologous CAR-T (definition: too few autologous lymphocytes [200/ML] or cannot meet the release standard); B) Experienced treatment with auto car-T/berintoomumab/ CD22 antibody conjugation drugs; C) ≥100 days after hematopoietic stem cell transplantation; D) high-risk patients (High risk was defined as a high white blood cell count ≥30×109/L at diagnosis or with poor cytogenetic prognosis);
  • Hypodiploid (<44 chromosomes);
  • KMT2A rearrangement: t (4;11) or otherwise;
  • t (v;q32)/IgH;
  • t (9;22) (q34;q11.2) or BCR-ABL1;
  • Complex karyotype (≥5 chromosomal abnormalities);
  • BCR-ABL1-like (Ph-like) ALL;
  • JAK-STAT (CRLF2r, EPORr, JAK1/2/3r, TYK2r, mutations of SH2B3, IL7r, Jak1/2/3 );
  • ABL class( rearrangement of ABL1, ABL2, PDGFRA, PDGFRB, FGFR);
  • Other (NTRKr, FLT3r, LYNr, PTK2Br);
  • Intrachromosomal amplification of chromosome 21 (IAMP21-ALL);
  • t (17;19) : TCF3-HLF fusion ;
  • Alterations of IKZF1; E) Extramedullary lesions.
• The expected survival time is ≥12 weeks;
• ECOG score 0-1;
• Had good organic function during screening
• CD19 was still expressed in leukemia cells in bone marrow, peripheral blood or biopsy tissue by flow cytometry within one month prior to informed consent (after the last treatment).