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Human CD19-CD22 Targeted T Cells Injection for Refractory/Relapsed Central Nervous System Leukemia/Lymphoma Patients

Primary Purpose

Central Nervous System Lymphoma

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Human CD19-CD22 Targeted T Cells Injection
Sponsored by
Hrain Biotechnology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Central Nervous System Lymphoma focused on measuring CD19-CD22, CAR-T, Central nervous system leukemia/lymphoma, Refractory/Relapsed

Eligibility Criteria

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

Inclusion Criteria:Subjects must meet all of the following criteria to be enrolled: B cell malignancies patients with CD19 or CD22 positive, or CD19 and CD22 positive,include B cell acute lymphoblastic leukemia relapsed with central nervous system invasion and refractory/relapsed B cell lymphoma of central nervous system; 18 to 70 years old (including cut-off value), Male and female; Expected survival > 12 weeks; ECOG score 0-2; Definitive diagnosed as central nervous system of B cell malignancies by Cerebrospinal fluid and/or MRI, PET/CT or other imaging examinations; The venous access required for collection can be established and leukapheresis can be carried according to the judgement of investigators; Liver, kidney and cardiopulmonary functions meet the following requirements: The detection value of Creatinine within the normal range; Left ventricular ejection fraction > 50%; Baseline oxygen saturation > 92%; Total bilirubin ≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; Able to understand and sign the Informed Consent Document. Exclusion Criteria:Any one of the following conditions cannot be selected as a subject: Malignant tumors other than B cell malignancies within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection; Subjects with positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer detection higher than or equal to the lower limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis detection positive; Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment; Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion; Received CAR-T treatment or other gene therapies before enrollment; Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell infusion; The investigators consider other conditions unsuitable for enrollment.

Sites / Locations

  • The Second Affiliated Hospital of Nanchang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Human CD19-CD22 Targeted T Cells Injection

Arm Description

Single administration: 1.0×10^6 CAR+T cells/kg, 3.0×10^6 CAR+T cells/kg, 5.0×10^6 CAR+T cells/kg

Outcomes

Primary Outcome Measures

Dose limited toxicity (DLT)
Safety Indicators
The occurrence rate of adverse events grade ≥ 3 assessed by NCI-CTCAE 5.0
Safety Indicators

Secondary Outcome Measures

Pharmacokinetics parameters - the highest concentration of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion
Effectiveness Metrics
Pharmacokinetics parameters - the time to reach the highest concentration of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion
Effectiveness Metrics
Pharmacokinetics parameters - the 28-day area under the curve of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion
Effectiveness Metrics
The rate of CAR-T cells in cerebrospinal fluid
Effectiveness Metrics
The duration of CAR-T cells in cerebrospinal fluid
Effectiveness Metrics
Pharmacodynamics characteristics - the detection values of IL-6, IFN-γ, IL-15 cytokines in peripheral blood
Effectiveness Metrics
Overall response rate (ORR) at 3 months after administration
Effectiveness Metrics
Duration of remission (DOR) after administration
Effectiveness Metrics
Overall Survival (OS) after administration
Effectiveness Metrics

Full Information

First Posted
December 2, 2022
Last Updated
December 13, 2022
Sponsor
Hrain Biotechnology Co., Ltd.
Collaborators
Second Affiliated Hospital of Nanchang University
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1. Study Identification

Unique Protocol Identification Number
NCT05651178
Brief Title
Human CD19-CD22 Targeted T Cells Injection for Refractory/Relapsed Central Nervous System Leukemia/Lymphoma Patients
Official Title
A Early Phase 1 Clinical Trial To Evaluate the Safety and Efficacy of Human CD19-CD22 Targeted T Cells Injection for Subjects With Central Nervous System Involvement of Refractory/Relapsed B Cell Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 12, 2022 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hrain Biotechnology Co., Ltd.
Collaborators
Second Affiliated Hospital of Nanchang University

4. Oversight

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

5. Study Description

Brief Summary
This study is a single-arm, open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of Human CD19-CD22 Targeted T Cells Injection, and to preliminarily observe the efficacy of the trial drug in patients with central nervous system involvement of refractory/relapsed B cell malignancies.
Detailed Description
Subjects with refractory/relapsed central nervous system involvement of B cell malignancies can participate if all eligibility criteria are met. Tests required to determine eligibility including disease assessments, a physical exam, Electrocardiograph, Computed tomography (CT) / Magnetic Resonance Imaging (MRI) / Positron Emission Tomography (PET), Cerebrospinal fluid exam and blood draws. Subjects will receive preconditioning chemotherapy prior to the infusion of Human CD19-CD22 Targeted T Cells Injection. After the infusion, subjects will be followed for adverse events, pharmacokinetic/pharmacodynamics characteristics, efficacy of Human CD19-CD22 Targeted T Cells Injection. Study procedures may be performed while hospitalized.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Central Nervous System Lymphoma
Keywords
CD19-CD22, CAR-T, Central nervous system leukemia/lymphoma, Refractory/Relapsed

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
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Human CD19-CD22 Targeted T Cells Injection
Arm Type
Experimental
Arm Description
Single administration: 1.0×10^6 CAR+T cells/kg, 3.0×10^6 CAR+T cells/kg, 5.0×10^6 CAR+T cells/kg
Intervention Type
Drug
Intervention Name(s)
Human CD19-CD22 Targeted T Cells Injection
Other Intervention Name(s)
CD19-CD22 CAR-T
Intervention Description
Autologous genetically modified anti-CD19/CD22 CAR transduced T cells
Primary Outcome Measure Information:
Title
Dose limited toxicity (DLT)
Description
Safety Indicators
Time Frame
28 days post infusion
Title
The occurrence rate of adverse events grade ≥ 3 assessed by NCI-CTCAE 5.0
Description
Safety Indicators
Time Frame
28 days post infusion
Secondary Outcome Measure Information:
Title
Pharmacokinetics parameters - the highest concentration of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Pharmacokinetics parameters - the time to reach the highest concentration of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Pharmacokinetics parameters - the 28-day area under the curve of Human CD19-CD22 Targeted T Cells amplified in peripheral blood after reinfusion
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
The rate of CAR-T cells in cerebrospinal fluid
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
The duration of CAR-T cells in cerebrospinal fluid
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Pharmacodynamics characteristics - the detection values of IL-6, IFN-γ, IL-15 cytokines in peripheral blood
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Overall response rate (ORR) at 3 months after administration
Description
Effectiveness Metrics
Time Frame
3 months post infusion
Title
Duration of remission (DOR) after administration
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Overall Survival (OS) after administration
Description
Effectiveness Metrics
Time Frame
2 years post 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 must meet all of the following criteria to be enrolled: B cell malignancies patients with CD19 or CD22 positive, or CD19 and CD22 positive,include B cell acute lymphoblastic leukemia relapsed with central nervous system invasion and refractory/relapsed B cell lymphoma of central nervous system; 18 to 70 years old (including cut-off value), Male and female; Expected survival > 12 weeks; ECOG score 0-2; Definitive diagnosed as central nervous system of B cell malignancies by Cerebrospinal fluid and/or MRI, PET/CT or other imaging examinations; The venous access required for collection can be established and leukapheresis can be carried according to the judgement of investigators; Liver, kidney and cardiopulmonary functions meet the following requirements: The detection value of Creatinine within the normal range; Left ventricular ejection fraction > 50%; Baseline oxygen saturation > 92%; Total bilirubin ≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; Able to understand and sign the Informed Consent Document. Exclusion Criteria:Any one of the following conditions cannot be selected as a subject: Malignant tumors other than B cell malignancies within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection; Subjects with positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer detection higher than or equal to the lower limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis detection positive; Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment; Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion; Received CAR-T treatment or other gene therapies before enrollment; Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell infusion; The investigators consider other conditions unsuitable for enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xuedong Sun, M.D.
Phone
0086-021-58552006
Email
sunxuedong@dashengbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qingming Wang, M.D.
Organizational Affiliation
Second Affiliated Hospital of Nanchang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qingming Wang, M.D.
Phone
0086-0791-86300483
Email
wqming222@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Human CD19-CD22 Targeted T Cells Injection for Refractory/Relapsed Central Nervous System Leukemia/Lymphoma Patients

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