crispr (hpk1) edited cd19-specific car-t cells (xyf19 car-t cells) for cd19+ leukemia or lymphoma.

Conditions: Leukemia Lymphocytic Acute (ALL) in Relapse; Leukemia Lymphocytic Acute (All) Refractory; Lymphoma, B-Cell; CD19 Positive

Summary: this is a first-in-human trial proposed to test cd19-specific car-t cells with edited endogenous hpk1 (xyf19 car-t cells) in patients with relapsed or refractory cd19+ leukemia or lymphoma. this is an investigational study designed as a single-center, open-label and single-arm clinical trial.


Eligibility criteria:
inclusion criteria: * subject must meet all the following criteria to be selected: 1. willing to provide consent/assent for participation in the study by patient or his/her legal guardian; 2. male or female subjects age ≥18 and ≤55 years; 3. evidence of relapsed/refractory cd19+ b cell hematological malignancies. the most common relapsed/refractory b cell hematological malignancies include: (1) b cell acute lymphoblastic leukemia (b-all); (2) b cell lymphomas, including indolent b cell lymphoma (cll, fl, mzl, lpl, hcl) and aggressive b cell lymphoma (dlbcl, bl, mcl)； 4. subjects (20 subjects of b cell acute lymphoblastic leukemia and 20 subjects of b cell lymphoma) with the following conditions: 1. failure to achieve complete remission (cr) after at least two lines of standard chemotherapy while not suitable for hsct (auto/allo-hsct)； 2. relapse after cr, but not eligible for hsct (auto/allo-hsct); 3. failure to achieve remission or relapse after hsct; 5. leukemia patient confirmed by bone marrow aspiration that has not been alleviated; lymphoma patient with measurable or assessable lesions; 6. adequate organ function: 1. liver: alt/ast ≥ 3 × uln, total bilirubin ≤34.2 mol/l; 2. kidney: creatinine\<220 µmol/l, creatinine clearance rate (ccr) ≥ 60 ml/min; 3. lung: arterial oxygen saturation ≥95%; 4. heart: left ventricular ejection fraction (lvef) ≥40%; 5. absolute lymphocyte count (alc) ≥ 100/μl, absolute neutrophil count (anc) ≥ 1,000/μl, platelets (plt) ≥ 75,000/μl; 7. no prior anti-cancer therapy, including chemotherapy, radiotherapy, immunotherapy (immunosuppression) within 4 weeks prior to enrollment, and toxic reactions of all prior treatments recovered to grade ≤1 at the time of enrollment (except for low toxicity such as alopecia); 8. presence of smooth peripheral superficial venous blood flow to fulfill intravenous infusion; 9. karnofsky performance score ≥60; ecog ≤2; estimated survival ≥3 months. exclusion criteria: * subjects meeting one or more of the following criteria will be excluded: 1. female patient who is pregnant or breastfeeding ; 2. male or female patient within pregnancy program in 1 year; 3. unwilling or unable to guarantee effective contraceptive measures (condoms or contraceptives) within 1 year after enrollment; 4. presence of uncontrolled infectious disease within 4 weeks prior to enrollment: 5. active hepatitis b or hepatitis c infection; 6. hiv infection; 7. active tb; 8. presence of active malignancy other than disease under study, confirmed by pathology; 9. severe autoimmune diseases or immunodeficiency; 10. suffering from allergies; 11. joining another clinical trial within 6 weeks prior to enrollment; 12. using systemic corticosteroid within 4 weeks prior to enrollment (except for those who use inhaled steroids); 13. psychiatric disorders; 14. history of epilepsy and seizures or other cns pathology; 15. addiction to or abuse of drugs; 16. presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol.

Keywords: leukemia lymphocytic acute lymphoma, b-cell