a study of universal cd19-targeted ucar-nk cells combined with hsct for b cell hematologic malignancies

Conditions: B-Cell Lymphoblastic Leukemia/Lymphoma

Summary: it is a single-center, open-labeled, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of anti-cd19 universal car-nk(ucar-nk) cells therapy combined with hsct for b cell hematologic malignancies.

who can participate? patients who were diagnosed with b cell hematologic malignancies and tumor cells expressing cd19. how to conduct this study? this study is an interventional clinical study. the intervention in the trial is anti-cd19 ucar-nk cells, which belong to chimeric antigen receptor modified nk cells. the administration time is 1-7 days after hematopoietic stem cell infusion. patients were then evaluated for long-term efficacy and safety until 2 years after ucar-nk cells infusion. what are the possible benefits and risks of participating? benefits: the dual effect of anti-tumor and anti-infection of nk cells may be used to promote the engraftment of hematopoietic stem cell and better disease control. risks: subjects may have adverse reactions to the treatment. these adverse reactions may include abnormal liver injury, fever, thrombocytopenia, thrombotic microangiopathy, and possibly other unknown adverse reactions.

Eligibility criteria:
inclusion criteria: 1. patients with indications for hematopoietic stem cell transplantation; 2. age ≤75 years old; 3. confirmed b-cell tumor and tumor cells expressing cd19； 4. expected survival time \>12 weeks; 5. eastern cooperative oncology group (ecog) score is 0-2; 6. adequate liver , kidney and cardiopulmonary function; 7. willingness to complete the informed consent process and to comply with study procedures and visit schedule. exclusion criteria: 1. had received nk cell therapy or other genetically modified cell therapy within 1 year before screening; 2. at least 14 days or at least 5 half-lives of antitumor therapy had elapsed before screening; 3. patients who had undergone hematopoietic stem cell transplantation (asct), allogeneic hematopoietic stem cell transplantation (hsct), or solid organ transplantation within 12 weeks before screening; grade 2 or higher graft versus host disease(gvhd) requiring immunosuppressive therapy occurred within 2 weeks before screening; 4. patients with atrial or ventricular lymphoma or need urgent treatment due to tumor mass such as intestinal obstruction or vascular compression; 5. have received live attenuated vaccine within 6 weeks before rinsing; 6. had a cerebrovascular accident or seizure within 6 months before screening; 7. history of deep venous thrombosis or pulmonary embolism within 6 months before screening; 8. a history of myocardial infarction, bypass or stent bypass, unstable angina, or other clinically significant heart disease within 12 months prior to screening; 9. previous history of alzheimer's disease; 10. autoimmune diseases leading to end-organ damage or requiring systemic immunosuppression (e.g. crohns, rheumatoid arthritis, systemic lupus erythematosus) within 2 years prior to screening; 11. there are uncontrollable infections; 12. women who are pregnant or breastfeeding; or women of childbearing age who have positive pregnancy tests during the screening period; male or female patients who did not wish to use contraception from the time of signing the informed consent to 1 year after receiving the nk cell infusion; 13. conditions that other researchers deemed inappropriate for participating in the study.

Keywords: universal car-nk(ucar-nk) hematopoietic stem cell transplantation(hsct)