clinical trial of hy004 cell injection in the treatment of relapsed or refractory b-cell non-hodgkin's lymphoma

Conditions: Non-hodgkin Lymphoma

Summary: this is a multi-center, open-label, single-arm, phase i/ii trial to evaluate the safety and efficacy of hy004 treatment in adult patients with relapsed or refractory b-cell non-hodgkin's lymphoma (r/r b-nhl).

this trial is a multi-center, open label, single-arm, phase i/ii trial to evaluate the safety and efficacy of hy004 in adult(aged 18\~75 years old) patients with r/r b-nhl. the phase i part of the trial is to evaluate the safety, optimal dose of hy004, pharmacokinetics/pharmacodynamics(pk/pd)and preliminary efficacy in the treatment of adult patients with r/r b-nhl. the phase ii part of the trial is to evaluate the efficacy and safety of hy004 in in the treatment of adult patients with r/r b-nhl. the study includes screening, pre-treatment (cell product manufacture \& lymphodepletion), hy004 infusion , safety and efficacy follow-up, and survival follow-up. all subjects who have received hy004 infusion will be followed for up to 2 years.

Eligibility criteria:
key inclusion criteria: 1. patients who are willing to sign the informed consent form; 2. aged 18-75 years, male or female; 3. previously received≥2nd-line adequate therapy or hematopoietic stem cell transplantation (hsct), and patients with cd19+/cd22+ relapsed/refractory b-nhl according to the who classification 2017, which are provided specifically as follows: 1. diffuse large b cell lymphoma (dlbcl), not otherwise specified (nos); 2. primary mediastinal large b cell lymphoma (pmbcl); 3. grade 3b follicular lymphoma; 4. transformed follicular lymphoma; 5. high grade b cell lymphoma with myc and bcl2 and/or bcl6 rearrangements, and high grade b cell lymphoma - not otherwise specified. 4. measurable imaging lesion at screening: intranodal lesion must have a long diameter of more than 1.5 cm, and extranodal lesion must have a long diameter of more than 1.0 cm with pet-positive disease by lugano classification . 5. pet-positive disease by lugano classification 6. adequate bone marrow, renal, hepatic, pulmonary and cardiac function. 7. adequate vascular access for leukapheresis procedure 8. subjects who have received previous cd19-targeted therapy must have cd19-positive lymphoma confirmed on a biopsy since completing the prior cd19-targeted therapy. key exclusion criteria: 1. active central nervous system (cns) involvement by malignancy. 2. patients with existing central nervous system disease or with a history of central nervous system disease. 3. patients receiving any of the following drugs or therapies within the specified period prior to apheresis: 1. alemtuzumab and bendamustine within 6 months prior to apheresis; 2. cladribine within 3 months prior to apheresis; 3. lenalidomide within 1 mouth prior to apheresis; 4. lymphocytotoxic chemotherapy within 2 weeks prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible; 5. anti-cd20 monoclonal antibody and therapeutic dose of hormones within 7 d prior to apheresis; 6. non-lymphocytotoxic chemotherapy within 7 d prior to apheresis - use in more than 3 half-lives prior to apheresis is eligible; 7. venetoclax (bcl-2 inhibitor) within 4 d prior to apheresis; 8. idelalisib (pi3kδ kinase inhibitor) within 2 d prior to apheresis; 9. dli within 6 weeks prior to apheresis; 10. radiotherapy within 6 weeks prior to apheresis - progressive disease at radiotherapy site, or pet positive lesion at other non-radiotherapy site is eligible; 4. patients previously received car-t cell therapy, the products that have same indication and have beenlisted in china are eligible; 5. patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-hsct) within 3 mouths. 6. patients with acute graft-versus-host disease (gvhd) or moderate-tosevere chronic gvhd within 4 weeks before screening. 7. active systemic autoimmune disease. 8. known infection with human immunodeficiency virus (hiv) or chronic infection with hepatitis b virus (hbsag positive) or hepatitis c virus (anti- hcv positive). 9. patients with active infections at screening. 10. history of cardiovascular disease. 11. pregnant or nursing women.

Keywords: hy004 cd22/cd19 chimeric antigen receptor t-cells