Back to resultsA Study of Universal CD19-Targeted UCAR-NK Cells Combined With HSCT for B Cell Hematologic Malignancies
Primary Purpose
B-Cell Lymphoblastic Leukemia/Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Anti-CD19 UCAR-NK cells
Sponsored by
About this trial
This is an interventional treatment trial for B-Cell Lymphoblastic Leukemia/Lymphoma focused on measuring universal CAR-NK(UCAR-NK), Hematopoietic Stem Cell Transplantation(HSCT)
Eligibility Criteria
Inclusion Criteria: Patients with indications for hematopoietic stem cell transplantation; Age ≤75 years old; Confirmed B-cell tumor and tumor cells expressing CD19； Expected survival time >12 weeks; Eastern cooperative oncology group (ECOG) score is 0-2; Adequate liver , kidney and cardiopulmonary function; Willingness to complete the informed consent process and to comply with study procedures and visit schedule. Exclusion Criteria: Had received NK cell therapy or other genetically modified cell therapy within 1 year before screening; At least 14 days or at least 5 half-lives of antitumor therapy had elapsed before screening; Patients who had undergone hematopoietic stem cell transplantation (ASCT), allogeneic hematopoietic stem cell transplantation (HSCT), or solid organ transplantation within 12 weeks before screening; Grade 2 or higher graft versus host disease(GVHD) requiring immunosuppressive therapy occurred within 2 weeks before screening; Patients with atrial or ventricular lymphoma or need urgent treatment due to tumor mass such as intestinal obstruction or vascular compression; Have received live attenuated vaccine within 6 weeks before rinsing; Had a cerebrovascular accident or seizure within 6 months before screening; History of deep venous thrombosis or pulmonary embolism within 6 months before screening; A history of myocardial infarction, bypass or stent bypass, unstable angina, or other clinically significant heart disease within 12 months prior to screening; Previous history of Alzheimer's disease; Autoimmune diseases leading to end-organ damage or requiring systemic immunosuppression (e.g. Crohns, rheumatoid arthritis, systemic lupus erythematosus) within 2 years prior to screening; There are uncontrollable infections; Women who are pregnant or breastfeeding; Or women of childbearing age who have positive pregnancy tests during the screening period; Male or female patients who did not wish to use contraception from the time of signing the informed consent to 1 year after receiving the NK cell infusion; Conditions that other researchers deemed inappropriate for participating in the study.
Sites / Locations
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of ChinaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Target CD19 UCAR-NK cells
Arm Description
Subjects who meet the enrollment conditions will receive intravenous infusion of anti-CD19 UCAR-NK Cells within 1 week after hematopoietic stem cell infusion.
Outcomes
Primary Outcome Measures
Incidence of adverse events(AE) after infusion
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
Secondary Outcome Measures
Granulocyte implantation time
Time from hematopoietic stem cell transfusion to peripheral blood granulocyte count >0.5×10^9/L for 3 consecutive days.
Platelet implantation time
Time from hematopoietic stem cell transfusion to peripheral blood platelet count >20×10^9/L for 7 consecutive days.
Red blood cell implantation time
Time from hematopoietic stem cell transfusion to peripheral blood hemoglobin count >70g/L.
Duration of remission (DOR)
Duration of remission (DOR) refers to the time from the first assessment of complete response(CR) or partial response(PR) of the tumor to the first assessment of disease recurrence or progression or death from any cause.
Disease control rate (DCR)
Disease control rate (DCR) are defined as the percentage of patients who have achieved complete response, partial response or stable disease to a therapeutic intervention in clinical trials of anticancer agents.
Overall survival (OS)
Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-NK cells until death (from any cause).
Progression-free survival (PFS)
Progression-free survival (PFS) refers to the time from the start of treatment with CAR-NK cells to the first progression of disease or death from any cause.
Full Information
NCT ID
NCT05654038
First Posted
December 7, 2022
Last Updated
December 19, 2022
Sponsor
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
1. Study Identification
Unique Protocol Identification Number
NCT05654038
Brief Title
A Study of Universal CD19-Targeted UCAR-NK Cells Combined With HSCT for B Cell Hematologic Malignancies
Official Title
An Investigator-initiated Trial Evaluating the Efficacy and Safety of Anti-CD19 Universal CAR-NK(UCAR-NK) Cells Therapy Combined With Hematopoietic Stem Cell Transplantation(HSCT) for B Cell Hematologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 8, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
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
It is a single-center, open-labeled, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of anti-CD19 universal CAR-NK(UCAR-NK) cells therapy combined with HSCT for B cell hematologic malignancies.
Detailed Description
Who can participate? Patients who were diagnosed with B cell hematologic malignancies and tumor cells expressing CD19.
How to conduct this study? This study is an interventional clinical study. The intervention in the trial is anti-CD19 UCAR-NK cells, which belong to chimeric antigen receptor modified NK cells. The administration time is 1-7 days after hematopoietic stem cell infusion. Patients were then evaluated for long-term efficacy and safety until 2 years after UCAR-NK cells infusion.
What are the possible benefits and risks of participating? Benefits: The Dual effect of anti-tumor and anti-infection of NK cells may be used to promote the engraftment of hematopoietic stem cell and better disease control.
Risks: Subjects may have adverse reactions to the treatment. These adverse reactions may include abnormal liver injury, fever, thrombocytopenia, thrombotic microangiopathy, and possibly other unknown adverse reactions.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-Cell Lymphoblastic Leukemia/Lymphoma
Keywords
universal CAR-NK(UCAR-NK), Hematopoietic Stem Cell Transplantation(HSCT)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Target CD19 UCAR-NK cells
Arm Type
Experimental
Arm Description
Subjects who meet the enrollment conditions will receive intravenous infusion of anti-CD19 UCAR-NK Cells within 1 week after hematopoietic stem cell infusion.
Intervention Type
Biological
Intervention Name(s)
Anti-CD19 UCAR-NK cells
Intervention Description
The trial includes two portions. The first portion is a"3+3"dose escalation study, in which three dose groups are set three different dose levels of UCAR-NK cells:Dose level one: 5-10×10^6/kg; Dose level two:1-2×10^7/kg; Dose level three:2-5×10^7/kg.
Primary Outcome Measure Information:
Title
Incidence of adverse events(AE) after infusion
Description
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
Time Frame
Up to 12 months after infusion
Secondary Outcome Measure Information:
Title
Granulocyte implantation time
Description
Time from hematopoietic stem cell transfusion to peripheral blood granulocyte count >0.5×10^9/L for 3 consecutive days.
Time Frame
Up to 1 month after infusion
Title
Platelet implantation time
Description
Time from hematopoietic stem cell transfusion to peripheral blood platelet count >20×10^9/L for 7 consecutive days.
Time Frame
Up to 1 month after infusion
Title
Red blood cell implantation time
Description
Time from hematopoietic stem cell transfusion to peripheral blood hemoglobin count >70g/L.
Time Frame
Up to 1 month after infusion
Title
Duration of remission (DOR)
Description
Duration of remission (DOR) refers to the time from the first assessment of complete response(CR) or partial response(PR) of the tumor to the first assessment of disease recurrence or progression or death from any cause.
Time Frame
Up to 24 weeks after infusion
Title
Disease control rate (DCR)
Description
Disease control rate (DCR) are defined as the percentage of patients who have achieved complete response, partial response or stable disease to a therapeutic intervention in clinical trials of anticancer agents.
Time Frame
Up to 24 weeks after infusion
Title
Overall survival (OS)
Description
Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-NK cells until death (from any cause).
Time Frame
Up to 24 weeks after infusion
Title
Progression-free survival (PFS)
Description
Progression-free survival (PFS) refers to the time from the start of treatment with CAR-NK cells to the first progression of disease or death from any cause.
Time Frame
Up to 24 weeks after infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with indications for hematopoietic stem cell transplantation;
Age ≤75 years old;
Confirmed B-cell tumor and tumor cells expressing CD19；
Expected survival time >12 weeks;
Eastern cooperative oncology group (ECOG) score is 0-2;
Adequate liver , kidney and cardiopulmonary function;
Willingness to complete the informed consent process and to comply with study procedures and visit schedule.
Exclusion Criteria:
Had received NK cell therapy or other genetically modified cell therapy within 1 year before screening;
At least 14 days or at least 5 half-lives of antitumor therapy had elapsed before screening;
Patients who had undergone hematopoietic stem cell transplantation (ASCT), allogeneic hematopoietic stem cell transplantation (HSCT), or solid organ transplantation within 12 weeks before screening; Grade 2 or higher graft versus host disease(GVHD) requiring immunosuppressive therapy occurred within 2 weeks before screening;
Patients with atrial or ventricular lymphoma or need urgent treatment due to tumor mass such as intestinal obstruction or vascular compression;
Have received live attenuated vaccine within 6 weeks before rinsing;
Had a cerebrovascular accident or seizure within 6 months before screening;
History of deep venous thrombosis or pulmonary embolism within 6 months before screening;
A history of myocardial infarction, bypass or stent bypass, unstable angina, or other clinically significant heart disease within 12 months prior to screening;
Previous history of Alzheimer's disease;
Autoimmune diseases leading to end-organ damage or requiring systemic immunosuppression (e.g. Crohns, rheumatoid arthritis, systemic lupus erythematosus) within 2 years prior to screening;
There are uncontrollable infections;
Women who are pregnant or breastfeeding; Or women of childbearing age who have positive pregnancy tests during the screening period; Male or female patients who did not wish to use contraception from the time of signing the informed consent to 1 year after receiving the NK cell infusion;
Conditions that other researchers deemed inappropriate for participating in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sanbin Wang, MD
Phone
13187424131
Ext
+86
Email
Sanbin1011@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sanbin Wang, MD
Organizational Affiliation
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Official's Role
Principal Investigator
Facility Information:
Facility Name
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chen Li
Phone
64774206
Ext
0871
12. IPD Sharing Statement
Learn more about this trial
A Study of Universal CD19-Targeted UCAR-NK Cells Combined With HSCT for B Cell Hematologic Malignancies
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