Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

NCT05667155 | Unknown Phase 1

• 1 other identifier: 2022-088
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

To study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with B-cell non-Hodgkin's lymphoma

Conditions

B-cell Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicity (DLTs)

  To evaluate the safety, tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma

  Up to 28 days

Secondary Outcomes (6)

• Overall survival (OS)

  Up to 2 years

• Overall response rate (ORR)

  Up to 2 years

• Duration of response (DOR)

  Up to 2 years

• Complete response rate (CR)

  Up to 2 years

• Partial response rate (PR)

  Up to 2 years

Study Arms (1)

CB dualCAR-NK19/70

EXPERIMENTAL

All subjects were intravenously administrated with CB dualCAR-NK19/70

Biological: CB dualCAR-NK19/70

Interventions

CB dualCAR-NK19/70 BIOLOGICAL

Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15

CB dualCAR-NK19/70

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the study and sign the informed consent;
• Age 18-75, male and female;
• Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other inert B-cell NHL transforming types:
• (1)refractory or recurrent DLBCL and tFL must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large B cell lymphoma (research SCHOLAR - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; The stable time of the disease is equal to or less than 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include CD20 single resistance (unless the subjects for CD20 negative) and anthracycline-based;
• \. There was at least one measurable lesion with the longest diameter ≥1.5 cm;
• \. Predicted survival ≥12 weeks;
• \. The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive;
• \. ECOG score 0-2;
• \. Adequate reserve of organ functions:
• cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit of normal);
• creatinine clearance (Cockcroft - Gault method) or 60 mL/min.
• serum total bilirubin and alkaline phosphatase (1.5 x or less UNL.
• glomerular filtration rate \> 50 mL/min
• heart ejection fraction (EF) 45% or higher;
• indoor natural air environment, basic oxygen saturation \> 92%

You may not qualify if:

• Allergic to any of the components of cell products;
• History of other tumors;
• Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; Or being treated with anti-GVHD;
• Had received gene therapy in the past 3 months;
• Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed;
• Subjects infected with hepatitis B (HBsAg positive, but HBV-DNA\<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons;
• Subjects with Grade III or IV cardiac insufficiency according to the New York Heart Association Cardiac Function Grading criteria;
• Patients who received antitumor therapy in the early stage but the toxicity reaction did not recover (CTCAE 5.0 toxicity reaction did not recover to ≤ level 1, except fatigue, anorexia and alopecia);
• Subjects with a history of epilepsy or other central nervous system diseases;
• Skull enhanced CT or MRI showing evidence of central nervous system lymphoma;
• Lactating women who refuse to stop breastfeeding;
• Any other circumstances that the investigator believes may increase the subject's risk or interfere with the test results.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hanzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Wenbin Wenbin

  2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenbin Qian, PhD

CONTACT

+8613605801032; qianwb@zju.edu.cn

Hui Liu, PhD

CONTACT

13819198629; sylen@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: December 28, 2022
• Study Start: December 15, 2022
• Primary Completion: January 1, 2025
• Study Completion: December 30, 2025
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)