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

Air Force Military Medical University of People's Liberation Army

Status and phase

Enrolling

Phase 1

Conditions

Leukemia Lymphocytic Acute (All) Refractory

Lymphoma, B-Cell

Leukemia Lymphocytic Acute (ALL) in Relapse

CD19 Positive

Treatments

Genetic: XYF19 CAR-T cell

Drug: Fludarabine

Drug: Cyclophosphamide

Study type

Interventional

Funder types

Other

Identifiers

NCT04037566

V2.1

Details and patient eligibility

About

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.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 55 years old

Volunteers

No Healthy Volunteers

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.