CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Male or female,≥18 years old;
* Histologically confirmed diagnosis of B-ALL or B-NHL(meeting one of the following conditions):

(B-NHL)

1. Second or greater relapse (CD20 regimens must be included) OR
2. Refractory to first-line chemotherapy or relapse within 1 year OR
3. Relapse within 1 year of auto-HSCT.
4. With measurable or evaluable lesions（Dose expansion cohort） (B-ALL)

a. Relapse within 12 months of complete remission on first treatment OR b. Relapse after second-line treatment OR c. Relapse after auto HST OR d. Failure to achieve CR/CRi at the end of induction therapy OR e. Ph+ ALL intolerance to TKI or refractory or relapse after treatment with at least two and more TKIs.

* ECOG 0\~2
* Estimated survival time ≥ 12 weeks;
* Main tissues and organs function well.

Exclusion Criteria:

* Subjects will be excluded related to the following prior therapy criteria:Prior treatment with bendamustine-containing or fludarabine;Anti-T-cell monoclonal antibody, donor lymphocyte infusion, and CNS radiotherapy within 8 weeks; Chemotherapy, lenalidomide, bortezomib within 2 weeks; vincristine within 1 week; glucocorticoids (prednisone ≥7.5 mg/d or equivalent) within 72 h
* Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
* Uncontrolled, symptomatic, intercurrent illness including but not limited to angina pectoris, cerebrovascular accident or transient ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association (NYHA) classification of ≥ Class III congestive heart failure, severe arrhythmia poorly controlled by medications, hepatic, renal, or metabolic disorders, and hypertension that is uncontrolled by standard therapy；
* active bleeding, or venous thromboembolic event
* Autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.) that result in end-organ damage or require systemic application of immunosuppressive drugs
* Central nervous system (CNS) disease or symptoms of CNS involvement
* Pregnant or nursing (lactating) women
* Presence of Grade 2 or above non-hematologic toxicity , alopecia and grade 2 neuropathy excluded
* Any Iinappropriate conditions in the opinion of the PI .

主要终点：Incidence of Dose-limiting toxicity · Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 · Up to 28 days；Incidence and severity of adverse events · Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 · Up to 15 years
次要终点：Overall response rate；Progression free survival；Overall survival；MRD negative response rates（ Acute Lymphoblastic Leukemia ）；Persistence of CD19/CD22 CAR-T cells blood, bone marrow

• Dose escalation · EXPERIMENTAL · CD19/CD22-CAR-transduced T cells at escalating doses (0.5\~5.0 ×10\^6 cells/kg)
• Dose expansion · EXPERIMENTAL · CD19/CD22-CAR-transduced T cells at MTD or highest dose administered

This study examines the safety, tolerability and preliminary efficacy of anti-CD19 /CD22 CAR T cells (KQ-2002)manufactured on-site in adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma.