Clinical Drug Experience Knowledgebase

Criteria

Criteria:

Inclusion Criteria:

Inclusion criteria applicable to ALL only:

Male or female aged ≥ 3 and <70 years old;
Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);

Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

CR not achieved after standardized chemotherapy;
CR achieved following the first induction, but CR duration is ≤ 12 months;
Ineffective after first or multiple remedial treatments;
2 or more recurrences;
The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (morphology) and/or >1% (Flow cytometry);
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:

Male or female aged ≥ 18 and <70 years old;
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;

Relapsed or refractory DLBCL (meeting one of the following conditions):

No remission or recurrence after receiving second-line or above second-line chemotherapy;
Primary drug resistance;
Recurrence after autologous hematopoietic stem cell transplantation;
According to Lugano 2014, there should be at least one evaluable tumor lesion.

Applicable standards for ALL and NHL:

HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-);
total bilirubin ≤ 51umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L;
Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
No active infection in the lungs, blood oxygen saturation by sucking air is ≥ 92%;
Estimated survival time ≥ 3 months;
ECOG performance status 0 to 2;
Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

patients with extramedullary lesions, except those with CNSL (CNS-1) under effective control (for ALL patients only);
Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);
Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (for ALL patients only);
Patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;
Extensive involvement of gastrointestinal lymphoma (for NHL patients only);
Radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;
Have a history of allergy to any of the components in the cell products;
Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency;
Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis).
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;

History of other primary cancer, except for the following conditions:

Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;
Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
Patients with graft-versus-host disease (GVHD);
Prior immunizations with live vaccine 4 weeks prior to screening;
History of alcoholism, drug abuse or mental illness;
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;
Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
Patients who have participated in any other clinical studies within 2 weeks prior to screening;
Pregnant and breast-feeding women and the subjects who are fertile and unable to take effective contraceptive measures (regardless of the gender);
Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.