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Safety and Efficacy of CD123-targeted CAR-NK for Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm

Primary Purpose

Acute Myeloid Leukemia, Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), Relapse Leukemia

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD123 targeted CAR-NK cells
Sponsored by
Chongqing Precision Biotech Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

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

Inclusion Criteria: Gender is not limited, age 18-75 years old (including the threshold value); The expression of CD123 in tumor cells was detected by flow cytometry. Patients with relapsed/refractory AML or BPDCN diagnosed with CD123 positive: 1) AML: a. Recurrent: After complete response (CR), the recurrence of leukemia cells in peripheral blood or bone marrow original cells ≥5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or the occurrence of extramedullary leukemia cell infiltration; b. Refractory: refers to those who have failed to receive 2 courses of treatment with standard protocols; Patients recurrence within 12 months after CR with consolidation and intensive treatment; Recurrence after 12 months but failed to respond to conventional chemotherapy; 2 or more relapses; Extramedullary leukemia persists; 2) BPDCN: has failed to receive guidelines-recommended salvage therapy or is unable to tolerate current therapy, and has persistent or recurrent disease in any of the peripheral blood, bone marrow, lymph nodes, spleen, skin lesions, or other site lesions. 4. Expected survival time is more than 12 weeks; 5. ECOG 0-2 points (Appendix 2); 6. No serious mental disorders; The functions of important organs are basically normal: Cardiac function: echocardiography indicated cardiac ejection fraction ≥50%, and no obvious abnormality was found in electrocardiogram; Renal function: serum creatinine ≤2.0×ULN; Liver function: ALT and AST ≤ 3.0×ULN; Total bilirubin and alkaline phosphatase ≤ 2.0×ULN (Gilbert syndrome ≤ 3.0×ULN); Blood oxygen saturation > 92%. 7. The patient or his/her guardian agrees to participate in the clinical trial and signs the ICF, indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study. Exclusion Criteria: Prior to screening, the following anti-tumor therapies were received: chemotherapy, targeted therapy, or other investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter), except in cases where disease progression has been confirmed after treatment; had a cerebrovascular accident or seizure within 6 months before signing the ICF; There is an active or uncontrolled infection that requires systemic treatment within 1 week prior to screening; suffering from any of the following heart diseases: New York Heart Association (NYHA) Stage III or IV congestive heart failure; Had myocardial infarction or coronary artery bypass grafting (CABG) within ≤6 months before enrollment; A history of clinically significant ventricular arrhythmia, or unexplained syncope (other than those caused by vasovagal or dehydration); History of severe non-ischemic cardiomyopathy; combined with active hepatitis B; Combined with active autoimmune diseases, long-term immunosuppressive therapy is required; have other malignancies, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery; Had received live attenuated vaccine within 4 weeks prior to screening; Women who are pregnant or breastfeeding, and male or female subjects who plan to have a family within 1 year after receiving CAR T cell transfusion; Circumstances deemed unsuitable for participation in the study by other researchers.

Sites / Locations

  • Shanxi Bethune HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Acute Myeloid Leukemia

Blastic Plasmacytoid Dendritic Cell Neoplasm

Arm Description

Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg

Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg

Outcomes

Primary Outcome Measures

To evaluate the safety of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Safety and Tolerability]
The incidence of adverse events after CD123 CAR-NK cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)
To evaluate the efficacy of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
Objective response rate at 4W±7D and 3M±7D after CAR-NK infusion (Objective response rate includes CR, CRi)

Secondary Outcome Measures

AUCS of CD123 CAR-NK cells [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
CMAX of CD123 CAR-NK cells [Cell dynamics]
CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
TMAX of CD123 CAR-NK cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Pharmacodynamics of CD123 CAR-NK cells[Cell dynamics]
The degree of clearance of malignant cells in peripheral blood was detected by blood smear at each time point,and the concentration level of serum cytoplasmic factors such as CRP and IL-6 were detected by ELISA at each time point

Full Information

First Posted
August 17, 2023
Last Updated
August 28, 2023
Sponsor
Chongqing Precision Biotech Co., Ltd
Collaborators
Shanxi Bethune Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06006403
Brief Title
Safety and Efficacy of CD123-targeted CAR-NK for Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm
Official Title
Clinical Study of Targeting CD123 Chimeric Antigen Receptor Natural Killer Cells (CAR-NK) in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
August 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chongqing Precision Biotech Co., Ltd
Collaborators
Shanxi Bethune Hospital

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-escalating + dose-expansion clinical study, aiming to evaluate the safety and efficacy of targeting CD123 CAR-NK cell preparations in Relapsed/refractory acute myeloid leukemia (AML) or blastocytic plasmacytoid dendritic cell neoplasm (BPDCN). The pharmacokinetic characteristics of CAR-NK cell preparations for the treatment of patients with Relapsed/refractory acute myeloid leukemia or blastocytic plasmacytoid dendritic cell neoplasm were obtained and the recommended dose.
Detailed Description
According to the different disease type, it is divided into two subgroups: AML and BPDCN. Each subgroup includes a dose exploration stage (Part A) and a dose expansion stage (Part B). 3 patients were explored, starting from the low-dose group, and in the dose expansion phase, the safety and efficacy were further verified according to the safe recommended dose obtained in the dose exploration phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), Relapse Leukemia, Refractory Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Acute Myeloid Leukemia
Arm Type
Experimental
Arm Description
Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg
Arm Title
Blastic Plasmacytoid Dendritic Cell Neoplasm
Arm Type
Experimental
Arm Description
Infusion of CD123-targeted CAR-NK cells by dose of 1-10x10^6 cells/kg
Intervention Type
Biological
Intervention Name(s)
CD123 targeted CAR-NK cells
Intervention Description
Administration method: intravenous infusion; Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
Primary Outcome Measure Information:
Title
To evaluate the safety of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Safety and Tolerability]
Description
The incidence of adverse events after CD123 CAR-NK cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)
Time Frame
1 month
Title
To evaluate the efficacy of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
Description
Objective response rate at 4W±7D and 3M±7D after CAR-NK infusion (Objective response rate includes CR, CRi)
Time Frame
1month,3months
Secondary Outcome Measure Information:
Title
AUCS of CD123 CAR-NK cells [Cell dynamics]
Description
AUCS is defined as the area under the curve in 90 days
Time Frame
3 months
Title
CMAX of CD123 CAR-NK cells [Cell dynamics]
Description
CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
Time Frame
3 months
Title
TMAX of CD123 CAR-NK cells[Cell dynamics]
Description
TMAX is defined as the time to reach the highest concentration
Time Frame
3 months
Title
Pharmacodynamics of CD123 CAR-NK cells[Cell dynamics]
Description
The degree of clearance of malignant cells in peripheral blood was detected by blood smear at each time point,and the concentration level of serum cytoplasmic factors such as CRP and IL-6 were detected by ELISA at each time point
Time Frame
3 months
Other Pre-specified Outcome Measures:
Title
Duration of Response (DOR) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
Description
DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause
Time Frame
2 years
Title
Progress-free survival(PFS) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
Description
PFS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause or the first assessment of progression
Time Frame
2 years
Title
Overall survival(OS)of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
Description
OS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause
Time Frame
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: Gender is not limited, age 18-75 years old (including the threshold value); The expression of CD123 in tumor cells was detected by flow cytometry. Patients with relapsed/refractory AML or BPDCN diagnosed with CD123 positive: 1) AML: a. Recurrent: After complete response (CR), the recurrence of leukemia cells in peripheral blood or bone marrow original cells ≥5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or the occurrence of extramedullary leukemia cell infiltration; b. Refractory: refers to those who have failed to receive 2 courses of treatment with standard protocols; Patients recurrence within 12 months after CR with consolidation and intensive treatment; Recurrence after 12 months but failed to respond to conventional chemotherapy; 2 or more relapses; Extramedullary leukemia persists; 2) BPDCN: has failed to receive guidelines-recommended salvage therapy or is unable to tolerate current therapy, and has persistent or recurrent disease in any of the peripheral blood, bone marrow, lymph nodes, spleen, skin lesions, or other site lesions. 4. Expected survival time is more than 12 weeks; 5. ECOG 0-2 points (Appendix 2); 6. No serious mental disorders; The functions of important organs are basically normal: Cardiac function: echocardiography indicated cardiac ejection fraction ≥50%, and no obvious abnormality was found in electrocardiogram; Renal function: serum creatinine ≤2.0×ULN; Liver function: ALT and AST ≤ 3.0×ULN; Total bilirubin and alkaline phosphatase ≤ 2.0×ULN (Gilbert syndrome ≤ 3.0×ULN); Blood oxygen saturation > 92%. 7. The patient or his/her guardian agrees to participate in the clinical trial and signs the ICF, indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study. Exclusion Criteria: Prior to screening, the following anti-tumor therapies were received: chemotherapy, targeted therapy, or other investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter), except in cases where disease progression has been confirmed after treatment; had a cerebrovascular accident or seizure within 6 months before signing the ICF; There is an active or uncontrolled infection that requires systemic treatment within 1 week prior to screening; suffering from any of the following heart diseases: New York Heart Association (NYHA) Stage III or IV congestive heart failure; Had myocardial infarction or coronary artery bypass grafting (CABG) within ≤6 months before enrollment; A history of clinically significant ventricular arrhythmia, or unexplained syncope (other than those caused by vasovagal or dehydration); History of severe non-ischemic cardiomyopathy; combined with active hepatitis B; Combined with active autoimmune diseases, long-term immunosuppressive therapy is required; have other malignancies, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery; Had received live attenuated vaccine within 4 weeks prior to screening; Women who are pregnant or breastfeeding, and male or female subjects who plan to have a family within 1 year after receiving CAR T cell transfusion; Circumstances deemed unsuitable for participation in the study by other researchers.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jia Wei, M.D
Phone
13986102084
Email
jiawei@tjh.tjmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jia Wei, M.D
Organizational Affiliation
Shanxi Bethune Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanxi Bethune Hospital
City
Taiyuan
State/Province
Shanxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jia Wei, MD

12. IPD Sharing Statement

Learn more about this trial

Safety and Efficacy of CD123-targeted CAR-NK for Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm

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