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

NCT ID: NCT04037566

Last Updated: 2019-07-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-31
• Study Completion Date: 2024-08-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

XYF19 CAR-T cell

One arm study consisting of "3 + 3" dose escalation study design followed by dose expansion phase at determined MTD.

Group Type: EXPERIMENTAL

XYF19 CAR-T cell

Intervention Type: GENETIC

Autologous T cells engineered to specify CD19 transduced with a lentiviral vector and electroporated with CRISPR guide RNA to disrupt expression of endogenous HPK1 administered by IV injection.

Cyclophosphamide

Intervention Type: DRUG

A cytotoxic chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.

Fludarabine

Intervention Type: DRUG

A chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.

Interventions

XYF19 CAR-T cell

Autologous T cells engineered to specify CD19 transduced with a lentiviral vector and electroporated with CRISPR guide RNA to disrupt expression of endogenous HPK1 administered by IV injection.

Intervention Type: GENETIC

Cyclophosphamide

A cytotoxic chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.

Intervention Type: DRUG

Fludarabine

A chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xi'An Yufan Biotechnology Co.,Ltd

UNKNOWN

Sponsor Role: collaborator

Xijing Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gao Guangxun

Director of Hematology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guangxun GAO, Dr.

Role: PRINCIPAL_INVESTIGATOR

Xijing Hospital

Locations

Xijing Hospital

Xi'an, Shannxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Guangxun GAO, Dr.

Role: CONTACT

gaoguangxun@fmmu.edu.cn

+86 29 84775203

Yu WANG, Dr.

Role: CONTACT

yu.wang@yufanbio.com

+86 29 88764122

Facility Contacts

Guangxun GAO, Dr.

Role: primary

gaoguangxun@fmmu.edu.cn

+86 29 84775203

Yu WANG, Dr.

Role: backup

yu.wang@yufanbio.com

+86 29 88764122

Other Identifiers

V2.1

Identifier Type: -

Identifier Source: org_study_id