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Anti-CD19 Universal CAR-NK Cells Therapy Combined With HSCT for B Cell Hematologic Malignancies

Primary Purpose

B-cell Lymphoma, B-cell Leukemia

Status

Withdrawn

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

anti-CD19 UCAR-NK cells

About this trial

This is an interventional treatment trial for B-cell Lymphoma focused on measuring universal CAR-NK, Hematopoietic Stem Cell Transplantation(HSCT)

Eligibility Criteria

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

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;
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 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

Kunming Hope of Health Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment group

Arm Description

Patients will get infused with anti-CD19 CAR-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 CR or 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

NCT05570188

First Posted

October 4, 2022

Last Updated

November 27, 2022

Sponsor

Kunming Hope of Health Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05570188

Brief Title

Anti-CD19 Universal CAR-NK Cells Therapy 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(U-CAR-NK) Cells Therapy Combined With Hematopoietic Stem Cell Transplantation(HSCT) for B Cell Hematologic Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Withdrawn

Why Stopped

The PI decides to stop.

Study Start Date

October 1, 2022 (Actual)

Primary Completion Date

October 31, 2024 (Anticipated)

Study Completion Date

October 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Kunming Hope of Health Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

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 U-CAR-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 U-CAR-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 U-CAR-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. Where is the study run? Kunming Hope of Health Hospital.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B-cell Lymphoma, B-cell Leukemia

Keywords

universal CAR-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

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment group

Arm Type

Experimental

Arm Description

Patients will get infused with anti-CD19 CAR-NK cells within 1 week after hematopoietic stem cell infusion.

Intervention Type

Biological

Intervention Name(s)

anti-CD19 UCAR-NK cells

Intervention Description

Enrolled participants are chosen to receive one of three different dose levels of U-CAR-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

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 CR or 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

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

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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; 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Li Li, MD

Organizational Affiliation

Kunming Hope of Health Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Kunming Hope of Health Hospital

City

Kunming

State/Province

Yunnan

ZIP/Postal Code

650000

Country

China

12. IPD Sharing Statement

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Anti-CD19 Universal CAR-NK Cells Therapy Combined With HSCT for B Cell Hematologic Malignancies

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