| Eligibility |
Inclusion Criteria:
Inclusion criteria applicable to ALL only:
1. Male or female aged = 3 and <70 years old;
2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive
Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia
(2016.v1);
3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):
1. CR not achieved after standardized chemotherapy;
2. CR achieved following the first induction, but CR duration is = 12 months;
3. Ineffective after first or multiple remedial treatments;
4. 2 or more recurrences;
4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5%
(morphology) and/or >1% (Flow cytometry);
5. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive
(Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI
treatments;
Inclusion criteria applicable to NHL only:
1. Male or female aged = 18 and <70 years old;
2. Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic
Tumors 2016, including DLBCL(NOS), follicular lymphoma, Chronic lymphoblastic
leukemia/small lymphoblastic lymphoma transforms DLBCL, PMBCL and high grade B cell
lymphoma;
3. Relapsed or refractory DLBCL (meeting one of the following conditions):
1. No remission or recurrence after receiving second-line or above second-line
chemotherapy;
2. Primary drug resistance;
3. Recurrence after autologous hematopoietic stem cell transplantation
4. According to Lugano 2014, there should be at least one evaluable tumor lesion.
Applicable standards for ALL and NHL:
1. HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-);
2. total bilirubin = 51umol/L, ALT and AST = 3 times of upper limit of normal, creatinine
= 176.8umol/L;
3. Echocardiogram shows left ventricular ejection fraction (LVEF) = 50%;
4. No active infection in the lungs, blood oxygen saturation by sucking air is = 92%;
5. Estimated survival time = 3 months;
6. ECOG performance status 0 to 2;
7. Patients or their legal guardians volunteer to participate in the study and sign the
informed consent.
Exclusion Criteria:
1. patients with extramedullary lesions, except those with CNSL (CNS-1) under effective
control (for ALL patients only);
2. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's
leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);
3. Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman
syndrome or any other known bone marrow failure syndrome (for ALL patients only);
4. patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells
and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;
5. extensive involvement of gastrointestinal lymphoma (for NHL patients only);
6. radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;
7. Have a history of allergy to any of the components in the cell products;
8. Prior treatment with any CAR T cell product or other genetically-modified T cell
therapies;
9. According to the New York heart association (NYHA) cardiac function classification
criteria, Subjects with grade III or IV cardiac insufficiency;
10. Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or
other severe cardiac diseases within 12 months of enrollment;
11. Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension
Guidelines, 1999);
12. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe
arrhythmia in the past;
13. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular
ischemia, and cerebrovascular hemorrhagic diseases;
14. Patients with severe active infections (excluding simple urinary tract infection and
bacterial pharyngitis).
15. Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct
catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated
central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;
16. History of other primary cancer, except for the following conditions:
1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
2. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with
disease-free survival = 2 years after adequate treatment;
17. Patients with autoimmune diseases requiring treatment, patients with immunodeficiency
or requiring immunosuppressive therapy;
18. Patients with graft-versus-host disease (GVHD);
19. Prior immunizations with live vaccine 4 weeks prior to screening;
20. History of alcoholism, drug abuse or mental illness;
21. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with
active hepatitis B > 1000 (if HBV DNA copy number=1000, routine antiviral therapy is
required after enrollment), as well as CMV, hepatitis C, syphilis infection;
22. Concurrent therapy with systemic steroids within 1 week prior to screening, except for
the patients recently or currently receiving inhaled steroids;
23. Patients who have participated in any other clinical studies within 2 weeks prior to
screening;
24. pregnant and breast-feeding women and the subjects who are fertile and unable to take
effective contraceptive measures (regardless of the gender);
25. Any situations that the investigator believes may increase the risk of patients or
interfere with the results of study.
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