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The Study of Anti-CD19 CAR NK Cells in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
anti-CD19 CAR NK cells
Sponsored by
Changhai Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring B-Cell Lymphoma, CD19, CAR-NK, diffuse diffuse large B cell lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF). Clinical diagnosis of CD19 positive diffuse large B cell lymphoma as defined by the 2017 World Health Organization (WHO) classification of tumors of haematopoietic and lymphoid tissue. Relapsed/Refractory diffuse large B cell lymphoma refers to: not complete response (CR) of 2 lines of standard treatment; PD after treatment or duration of SD less than 6 months after treatment; progress or relapse within 12 months after autologous stem cell transplant. Subjects with a measurable or evaluable lesion (more than one lesion≥15mm) according to IWG criteria. Age≥ 18 years old and ≤ 75 years old, male or female. Subjects with estimated survival > 12 weeks. Serum albumin (ALB) ≥30g/L, Total Bilirubin (TBIL) ≤ 25.7μmol/L, serum creatinine (SCr) ≤ 132.6μmol/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN). Absolute neutrophil count (ANC) ≥ 1.0×109/L, platelet count ≥ 50×109/L. ECOG performance ≤ 1. Left ventricular ejection fraction (LVEF) ≥50% and no clinically significant pericardial effusion. ≥ 4 weeks after subjects received last dose treatment (Radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments). Exclusion Criteria: Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions. Relapsed after allogenic haemopoietic stem cell transplantation (HSCT). Subjects with active infection receiving intravenous (IV) antibiotic treatment, or received intravenous (IV) antibiotic treatment within one week prior to anti-CD19 CAR NK Cell infusion. Subjects with acquired and congenital immunodeficiency diseases. Subjects with grade III or IV heart failure (NYHA classification). History of epilepsy or other central nervous system (CNS) diseases. Subjects with extranodal lymphoma in Intracranial, lung, or gastrointestinal tract. History of other primary malignant tumors except: Cured non-melanoma skin cancer by surgical excision, for example basal cell carcinoma (BCC); Cured primary malignant tumors, such as cervical cancer, superficial bladder cancer, breast cancer. Systemic corticosteroids are used concomitantly within 2 weeks prior to treatment. Females who are pregnant, lactating, or planning a pregnancy within six months. Subjects who have received other clinical trial treatment within 3 months. Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome.

Sites / Locations

  • Changhai HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-CD19 CAR NK cells

Arm Description

CD19-CAR-NK is an allogenic CD19-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicity (DLTs)
To characterize the safety, tolerability, and determine the Maximum tolerated dose (MTD) of Anti-CD19 CAR NK Cells for Relapsed/Refractory diffuse large B cell lymphoma.
Incidence of Treatment Emergent Adverse Events (TEAEs)
To characterize the safety of Anti-CD19 CAR NK Cells for Relapsed/Refractory diffuse large B cell lymphoma

Secondary Outcome Measures

The overall response rate (ORR)
To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for Relapsed/Refractory diffuse large B cell lymphoma
Disease control rate (DCR)
To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for R/R Non-Hodgkin Lymphoma.

Full Information

First Posted
December 21, 2022
Last Updated
August 25, 2023
Sponsor
Changhai Hospital
Collaborators
Nanjing Enricnk Biotech Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05673447
Brief Title
The Study of Anti-CD19 CAR NK Cells in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma
Official Title
An Exploratory Clinical Study of Safety and Efficacy of Anti-CD19 CAR NK Cells in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Changhai Hospital
Collaborators
Nanjing Enricnk Biotech Co., Ltd

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
A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cells in patients with B-cell Non Hodgkin Lymphoma. 9-12 patients are planned to be enrolled in the dose-escalation trial (6×10^8 cells, 1×10^9 cells, 1.5×10^9 cells). The primary endpoints are DLT, MTD. The secondary endpoints are the overall response rates (ORR) and disease control rate (DCR).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma
Keywords
B-Cell Lymphoma, CD19, CAR-NK, diffuse diffuse large B cell lymphoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
anti-CD19 CAR NK cells
Arm Type
Experimental
Arm Description
CD19-CAR-NK is an allogenic CD19-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.
Intervention Type
Biological
Intervention Name(s)
anti-CD19 CAR NK cells
Intervention Description
Patients will receive Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Doses of 6×10^8, 1×10^9, 1.5×10^9 Anti-CD19 CAR NK cells will infused in each group using the "3 + 3" dose-escalation strategy.
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicity (DLTs)
Description
To characterize the safety, tolerability, and determine the Maximum tolerated dose (MTD) of Anti-CD19 CAR NK Cells for Relapsed/Refractory diffuse large B cell lymphoma.
Time Frame
within 4 weeks after infusion
Title
Incidence of Treatment Emergent Adverse Events (TEAEs)
Description
To characterize the safety of Anti-CD19 CAR NK Cells for Relapsed/Refractory diffuse large B cell lymphoma
Time Frame
up to 48 weeks after infusion
Secondary Outcome Measure Information:
Title
The overall response rate (ORR)
Description
To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for Relapsed/Refractory diffuse large B cell lymphoma
Time Frame
1, 3, 6 and 12 months after infusion
Title
Disease control rate (DCR)
Description
To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for R/R Non-Hodgkin Lymphoma.
Time Frame
1, 3, 6, 12 and 12 months after infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF). Clinical diagnosis of CD19 positive diffuse large B cell lymphoma as defined by the 2017 World Health Organization (WHO) classification of tumors of haematopoietic and lymphoid tissue. Relapsed/Refractory diffuse large B cell lymphoma refers to: not complete response (CR) of 2 lines of standard treatment; PD after treatment or duration of SD less than 6 months after treatment; progress or relapse within 12 months after autologous stem cell transplant. Subjects with a measurable or evaluable lesion (more than one lesion≥15mm) according to IWG criteria. Age≥ 18 years old and ≤ 75 years old, male or female. Subjects with estimated survival > 12 weeks. Serum albumin (ALB) ≥30g/L, Total Bilirubin (TBIL) ≤ 25.7μmol/L, serum creatinine (SCr) ≤ 132.6μmol/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN). Absolute neutrophil count (ANC) ≥ 1.0×109/L, platelet count ≥ 50×109/L. ECOG performance ≤ 1. Left ventricular ejection fraction (LVEF) ≥50% and no clinically significant pericardial effusion. ≥ 4 weeks after subjects received last dose treatment (Radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments). Exclusion Criteria: Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions. Relapsed after allogenic haemopoietic stem cell transplantation (HSCT). Subjects with active infection receiving intravenous (IV) antibiotic treatment, or received intravenous (IV) antibiotic treatment within one week prior to anti-CD19 CAR NK Cell infusion. Subjects with acquired and congenital immunodeficiency diseases. Subjects with grade III or IV heart failure (NYHA classification). History of epilepsy or other central nervous system (CNS) diseases. Subjects with extranodal lymphoma in Intracranial, lung, or gastrointestinal tract. History of other primary malignant tumors except: Cured non-melanoma skin cancer by surgical excision, for example basal cell carcinoma (BCC); Cured primary malignant tumors, such as cervical cancer, superficial bladder cancer, breast cancer. Systemic corticosteroids are used concomitantly within 2 weeks prior to treatment. Females who are pregnant, lactating, or planning a pregnancy within six months. Subjects who have received other clinical trial treatment within 3 months. Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianmin Yang, Ph. D.
Phone
13918735105
Email
chyangjianmin@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Libing Wang, Ph.D.
Phone
13918735105
Email
doctorwanglibing@126.com
Facility Information:
Facility Name
Changhai Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianmin Yang, Doctor
Phone
86-18317172636
Email
yangjianmin@csco.org.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

The Study of Anti-CD19 CAR NK Cells in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

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