relmacabtagene autoleucel as first-line therapy for high-risk large b-cell lymphoma

Conditions: B-cell Lymphoma

Summary: the primary objective of this study is to estimate the efficacy of relmacabtagene autoleucel in participants with high-risk large b-cell lymphoma.

this is a prospective, open-label, multicenter, single-arm trial, assessed the efficacy and safety of jwcar029(relma-cel) as part of first-line therapy after an incomplete first-line treatment regimen of two cycles of chemoimmunotherapy. high-risk lbcl was defined by the dynamic risk assessment of interim pet2+, together with either double- or triple-hit lymphomas or high-intermediate- and high-risk ipi scores (≥3). all sujects will be followed for 2 years following jwcar029 infusion.

Eligibility criteria:
inclusion criteria: 1. ≥ 18 years old; 2. sign on the informed consent; 3. histologically confirmed large b-cell lymphoma that also meets the definition of high-risk large b-cell lymphoma as a lymphoma international prognostic index (ipi) score of 3-5 and/or high-grade b-cell lymphoma with myc and bcl2 and/or bcl6 rearrangement (double/triple-hit lymphoma) (dhl/thl) and must be treated with 2 cycles of cd20 monoclonal antibodies combined with anthracyclines. presence of positive pet assessable lesions (ds score of 4 or 5) as determined by the lugano criteria (cheson et al., 2014)； 4. eastern cooperative oncology group (ecog) performance status of 0 or 1; 5. expected survival greater than 12 weeks； 6. adequate organ function： 1. absolute neutrophil count ≥ 1000/μl；absolute lymphocyte count ≥ 100/μl； platelet count ≥ 75,000/μl；hb ≥ 80g/l； 2. serum creatinine ≤ 1.5 × upper limit of normal (uln) or creatinine clearance (cockcroft-gault formula) \> 50 ml/min (serum creatinine clearance due to lymphoma mass compression should be \> 30 ml/min)； 3. serum alanine aminotransferase (alt) ≤ 5 upper limit of normal (uln) and total bilirubin ≤2uln（or for subjects with gilbert's syndrome or lymphoma invading the liver \< 3 uln）； 4. baseline oxygen saturation \> 92% on room air； 5. left ventricular ejection fraction (lvef) ≥50% assessed by echocardiography or radionuclide activity angiography (muga) within 1 month of enrollment； 7. adequate vascular access for leukapheresis procedure; 8. women of childbearing potential must agree to use highly effective methods of contraception for at least 28 days prior to lymphocyte clearance chemotherapy through 1 year after relmacabtagene autoleucel infusion; males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after relmacabtagene autoleucel infusion. exclusion criteria: 1. lymphoma involving the central nervous system (cns)； 2. history of another primary malignancy that has not been in remission for at least 2 years; 3. history of richter's transformation of chronic lymphocytic leukemia or primary mediastinal b-cell lymphoma； 4. subjects has hbv, hcv, hiv or syphilis infection at the time of screening; 5. deep venous thrombosis (dvt)/pulmonary embolism (pe), or dvt/pe requires anti-coagulation within 3 months prior to signing the icf; 6. subjects with uncontrolled systemic fungal, bacterial, viral or other infection; 7. presence of acute or chronic graft-versus-host disease (gvhd); 8. history of any serious cardiovascular disease or presence of clinically relevant cns pathology; 9. pregnant or nursing women; 10. subjects received an autologous or allogeneic hematopoietic stem cell transplant； 11. uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol; 12. received car t-cell or other genetically-modified t-cell therapy previously； 13. received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy； 14. history of severe hypersensitivity reactions to any of the drug ingredients used in this study product.