a study of ct-rd06 cell injection in patients with relapsed or refractory cd19+ b-cell hematological malignancy

Conditions: Acute Lymphoblastic Leukemia; Non-Hodgkin's Lymphoma

Summary: a study of ct-rd06 cell injection in patients with relapsed or refractory cd19+ b-cell hematological malignancy.

this is a single arm, open-label, single-center study. this study is indicated for relapsed or refractory cd19+ b-cell hematological malignancy: b-all and b-nhl, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 2 groups of patients will be enrolled, 36 in each group. primary objective is to explore the safety, main consideration is dose-related safety.

Eligibility criteria:
inclusion criteria: * inclusion criteria only for b-all: 1. male or female aged 3-70 years; 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. ineffectively after first or multiple remedial treatments; 4. 2 or more relapses; 4. the number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is﹥5% (by morphology), and/or﹥1% (by 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 only for b-nhl: 1. male or female aged 18-70 years; 2. histologically confirmed diagnosis of dlbcl (nos), fl, dlbcl transformed from cll/sll, pmbcl, and hgbcl per the who classification criteria for lymphoma (2016); 3. relapsed or refractory b-nhl (meeting one of the following conditions): 1. no response or relapse after second-line or above chemotherapy regimens; 2. primary drug resistance; 3. relapse after auto-hsct; 4. at least one assessable tumor lesion per lugano 2014 criteria; * common inclusion criteria for b-all and b-nhl: 1. total bilirubin ≤ 51 umol/l, alt and ast ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/l; 2. echocardiogram shows left ventricular ejection fraction (lvef) ≥ 50%; 3. no active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%; 4. estimated survival time ≥ 3 months; 5. ecog performance status 0 to 2; 6. patients or their legal guardians volunteer to participate in the study and sign the informed consent. exclusion criteria: * inclusion exclusion criteria only for b-all: 1. extramedullary lesions, except that cnsl (cns-1) has been effectively controlled; 2. confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, burkitt's leukemia/ lymphoma per who classification criteria; 3. hereditary syndrome such as fanconi anemia, kostmann syndrome, shwachman syndrome or any other known bone marrow failure syndrome; * inclusion exclusion criteria only for b-nhl: 1. extranodal lesions in the brain (tumor cells in csf, and/or mri shows invasion of intracranial lymphoma); 2. extensive invasion of gastrointestinal lymphoma; * common exclusion criteria for b-all and b-nhl: 1. history of hypersensitivity to any component of cell product; 2. prior treatment with any car t cell product or other genetically-modified t cell therapies; 3. prior treatment with radiotherapy, chemotherapy or mab 1 week prior to apheresis; 4. new york heart associate (nyha) class iii/iv cardiac insufficiency (see appendix 1); 5. myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment; 6. severe primary or secondary hypertension of grade 3 or above (who hypertension guidelines, 1999); 7. electrocardiogram shows prolonged qt interval, severe heart diseases such as severe arrhythmia in the past; 8. history of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; 9. severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); 10. 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; 11. 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; 12. autoimmune diseases requiring treatment, immunodeficiency or patients requiring immunosuppressive therapy; 13. prior immunizations with live vaccine 4 weeks prior to screening; 14. history of alcoholism, drug abuse or mental illness; 15. 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 and hiv infection; 16. concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids; 17. patients who have participated in any other clinical studies within 2 weeks prior to screening; 18. female pregnant or lactating, male for female fertile but unable to take medically acceptable contraception measures; 19. any situations that the investigator believes may increase the risk of patients or interfere with the results of study.