Clinical trial NCT04037566: CRISPR (HPK1) Edited CD19-specific CAR-T Cells (XYF19 CAR-T Cells) for CD19+ Leukemia or Lymphoma.
Official title: A Safety Study of Autologous T Cells Engineered to Target CD19 and CRISPR Gene Edited to Eliminate Endogenous HPK1 (XYF19 CAR-T Cells) for Relapsed or Refractory Haematopoietic Malignancies.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Leukemia Lymphocytic Acute (ALL) in Relapse
Leukemia Lymphocytic Acute (All) Refractory
Lymphoma, B-Cell
CD19 Positive
Keywords: Leukemia Lymphocytic Acute
Lymphoma, B-Cell
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
Collaborators: name: Xi'An Yufan Biotechnology Co.,Ltd
First posted: 2019-07-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: The adverse events associated with XYF19 CAR-T cells product will be assessed.
timeFrame: 30 days
measure: Maximum tolerated dose (MTD) as determined by dose limiting toxicity (DLT).
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xijing Hospital
state: Shannxi
Study officials:
affiliation: Xijing Hospital
name: Guangxun GAO, Dr.
role: PRINCIPAL_INVESTIGATOR
References: