CRISPR (HPK1) Edited CD19-specific CAR-T Cells (XYF19 CAR-T Cells) for CD19+ Leukemia or Lymphoma.

• Status: Recruiting
• Trial end date: 2024-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Xijing Hospital
• Collaborator: Xi'An Yufan Biotechnology Co.,Ltd
• Treatments: Cyclophosphamide; Fludarabine

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.