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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- B-cell Lymphoma
- Sponsor
- Kunming Hope of Health Hospital
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events(AE) after infusion
- Status
- Withdrawn
- Last Updated
- 3 years ago
Overview
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.
Investigators
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;
Outcomes
Primary Outcomes
Incidence of adverse events(AE) after infusion
Time Frame: Up to 12 months 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 Outcomes
- Duration of remission (DOR)(Up to 24 weeks after infusion)
- Granulocyte implantation time(Up to 1 month after infusion)
- Platelet implantation time(Up to 1 month after infusion)
- Red blood cell implantation time(Up to 1 month after infusion)
- Disease control rate (DCR)(Up to 24 weeks after infusion)
- Overall survival (OS)(Up to 24 weeks after infusion)
- Progression-free survival (PFS)(Up to 24 weeks after infusion)