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

Primary Purpose

B-cell Non Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CB dualCAR-NK19/70
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Non Hodgkin Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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; 4. There was at least one measurable lesion with the longest diameter ≥1.5 cm; 5. Predicted survival ≥12 weeks; 6. The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive; 7. ECOG score 0-2; 8. 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% blood routine: neutrophils absolute number > 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin; 9. Allowed to have received a previous stem cell transplant 10. Approved anti-B-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. The eluting period of targeted drug regimens without chemotherapy was 2 weeks; 11. Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted; 12. Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial 13. Two tests have come back negative for COVID-19. Exclusion Criteria: 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.

Sites / Locations

  • 2nd Affiliated Hospital, School of Medicine, Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CB dualCAR-NK19/70

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall survival (OS)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Overall response rate (ORR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Duration of response (DOR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Complete response rate (CR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Partial response rate (PR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Progression free survival (PFS)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70

Full Information

First Posted
November 29, 2022
Last Updated
February 2, 2023
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT05667155
Brief Title
Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma
Official Title
Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2022 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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
Detailed Description
This is a single-center, open, one-arm, dose-escalation study to observe the safety and efficacy of cord blood-derived dualCAR-NK19/70 cells in patients with B-cell non-Hodgkin lymphoma.9-18 patients are planned to be enrolled in the dose-escalation trial (2×10^6 cells/kg, 4×10^6 cells/kg, 8×10^6 cells/kg) . Each dose was given once a week for 3 weeks.The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled to estimate the safety and efficacy of CB CAR-NK019 under the best dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Non Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CB dualCAR-NK19/70
Arm Type
Experimental
Arm Description
All subjects were intravenously administrated with CB dualCAR-NK19/70
Intervention Type
Biological
Intervention Name(s)
CB dualCAR-NK19/70
Intervention Description
Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicity (DLTs)
Description
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
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Time Frame
Up to 2 years
Title
Overall response rate (ORR)
Description
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Time Frame
Up to 2 years
Title
Duration of response (DOR)
Description
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Time Frame
Up to 2 years
Title
Complete response rate (CR)
Description
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Time Frame
Up to 2 years
Title
Partial response rate (PR)
Description
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Time Frame
Up to 2 years
Title
Progression free survival (PFS)
Description
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; 4. There was at least one measurable lesion with the longest diameter ≥1.5 cm; 5. Predicted survival ≥12 weeks; 6. The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive; 7. ECOG score 0-2; 8. 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% blood routine: neutrophils absolute number > 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin; 9. Allowed to have received a previous stem cell transplant 10. Approved anti-B-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. The eluting period of targeted drug regimens without chemotherapy was 2 weeks; 11. Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted; 12. Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial 13. Two tests have come back negative for COVID-19. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenbin Qian, PhD
Phone
+8613605801032
Email
qianwb@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Liu, PhD
Phone
13819198629
Email
sylen@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenbin Wenbin
Organizational Affiliation
2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
2nd Affiliated Hospital, School of Medicine, Zhejiang University
City
Hanzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenbin Qian, PhD
Phone
+8613605801032
Email
qianwb@zju.edu.cn
First Name & Middle Initial & Last Name & Degree
Hui Liu, PhD
Phone
13819198629
Email
sylen@zju.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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