Senl_1904A and Senl_1904B Chimeric Antigen Receptor （CAR） T-Cell in the Treatment of r/ r Acute B Lymphocytic Leukemia

This is an interventional treatment trial for Acute Lymphocytic Leukemia Read More

Inclusion Criteria:

• Subjects with acute lymphocytic leukemia who voluntarily signed informed consent and met the following criteria:

  1. Patients with relapsed and refractory acute B lymphocytic leukemia with any of the following:

     1. Recurrence after remission by chemotherapy or autologous stem cell transplantation (including B-ALL patients with bone marrow recurrence of morphology and recurrence of micro-residual );
     2. Primary B-ALL patients who cannot be completely relieved by repeated chemotherapy twice or more;
     3. High-risk initial onset B-ALL patients not completely relieved after 1 or 2 times of chemotherapy but not suitable for re-chemotherapy ;
  2. Tumor cells confirmed CD19 positive by Flow cytometry (FCM)
  3. For B-ALL patients with simple extramedullary recurrence , there must be at least one evaluable lesion;
  4. Eastern Cooperative Oncology Group (ECOG) ≤ 2 points;
  5. Age 3 - 65 years old;
  6. The bone marrow tumor load value (morphology) > 5% at the time of enrollment;
  7. The main organ function needs to meet the above conditions: cardiac ultrasound or multiple gated image acquisition analysis （MUGA） scan indicate the cardiac ejection fraction is ≥50% , and there is no obvious abnormality in the electrocardiogram; blood oxygen saturation≥90%; creatinine ≤1.6mg/dl; alanine amino transferase (ALT) and Aspartate transaminase (AST)≤3 times normal range, total bilirubin（TBil） ≤2.0mg/dl;
  8. The expected survival time is longer than 3 months;
  9. The pregnancy test for women of childbearing age must be negative; Subjects with a pregnancy plan must agree to take contraception before the enrollment study and after the study lasts for one year; if the subject is pregnant or suspects of pregnancy, the investigator should be notified immediately
  10. An informed consent form is required.

Exclusion Criteria:

• 1) Severe cardiac insufficiency; 2) A history of severe pulmonary dysfunction; 3) Combined with other malignant tumors; 4) Combined with serious infections or persistent infection and cannot be effectively controlled; 5) Combined with metabolic diseases (except DM); 6) Combined with severe autoimmune diseases or congenital immune defects; 7) Active hepatitis (HBV DNA or HCVRNA detection positive); 8) HIV infection or syphilis infection; 9) A history of severe allergies to biological products (including antibiotics); 10) Subjects with recurrence after allogeneic hematopoietic stem cell transplantation 11) chronic lymphocytic leukemia（CLL） /myeloproliferative neoplasms with acute lymphoid transformation or CLL transform to ALL ; 12) Any drug that has been used against graft-versus-host disease（GVHD） for nearly 4 weeks, such as methotrexate or other chemotherapeutic drugs, mycophenolate mofetil, immunosuppressive antibodies, etc.; 13) Subjects who have received any anti-CD19 medication; 14) Subjects who have used anti-cluster of differentiation antigen 20（CD20） drugs (such as rituximab) for nearly 4 weeks; 15) Subjects who have participated in any other clinical drug trials in the past six months; 16) Female patients who are pregnant and lactating, or have a pregnancy plan within 12 months; 17) The investigator believes that it may increase the risk of the subject or interfere with the outcome of the test (with a history of severe mental illness, drug abuse and history of addiction).

Exit criteria：

1. The subjects request to withdraw from the study before CAR-T infusion
2. The subjects seriously violate the protocol

3. Before CAR-T infusion, the following indicators are still abnormal after treatment:

   Platelets <20x10^9/L, hemoglobin ≤80g/L, peripheral finger oxygen <90%, AST / ALT / alkaline phosphatase（ALP） ≥ 2.5 upper limits of normal（ULN）, total bilirubin ≥ 1.5ULN , creatinine clearance rate <70ml / min, left ventricular ejection fraction <50%, the researcher judged that the test needs to be terminated early;

4. The therapeutic dose of steroids was not stopped within 72 hours prior to CAR-T infusion and the investigator determined that the trial needs to be terminated . However, the following physiologically acceptable doses of steroids are permissible: hydrocortisone or equivalent <6-12 mg/m2/day ;
5. Not enough T cells for manufacture standard CAR-T cells
6. Other serious adverse events occurred
7. MRD become negative after preconditioning regiment