Clinical trial NCT05570188: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: B-cell Lymphoma
B-cell Leukemia
Keywords: universal CAR-NK
Hematopoietic Stem Cell Transplantation(HSCT)
Lead sponsor: Kunming Hope of Health Hospital
Sponsor class: OTHER
First posted: 2022-10-06
Enrollment: 0
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Patients with indications for hematopoietic stem cell transplantation;
2. Age ≤75 years old;
3. Confirmed B-cell tumor and tumor cells expressing CD19；
4. Expected survival time \>12 weeks;
5. ECOG score is 0-2;
6. Adequate liver , kidney and cardiopulmonary function;
7. Willingness to complete the informed consent process and to comply with study procedures and visit schedule.

Exclusion Criteria:

1. Had received NK cell therapy or other genetically modified cell therapy within 1 year before screening;
2. At least 14 days or at least 5 half-lives of antitumor therapy had elapsed before screening;
3. 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;
4. Patients with atrial or ventricular lymphoma or need urgent treatment due to tumor mass such as intestinal obstruction or vascular compression;
5. Have received live attenuated vaccine within 6 weeks before rinsing;
6. Had a cerebrovascular accident or seizure within 6 months before screening;
7. History of deep venous thrombosis or pulmonary embolism within 6 months before screening;
8. A history of myocardial infarction, bypass or stent bypass, unstable angina, or other clinically significant heart disease within 12 months prior to screening;
9. Previous history of Alzheimer's disease;
10. 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;
11. There are uncontrollable infections;
12. 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;
13. Conditions that other researchers deemed inappropriate for participating in the study.

Primary outcomes:
measure: Incidence of adverse events(AE) after infusion
timeFrame: Up to 12 months after infusion
Secondary outcomes:
measure: Granulocyte implantation time
timeFrame: Up to 1 month after infusion
measure: Platelet implantation time
timeFrame: Up to 1 month after infusion
measure: Red blood cell implantation time
timeFrame: Up to 1 month after infusion
measure: Duration of remission (DOR)
timeFrame: Up to 24 weeks after infusion
measure: Disease control rate (DCR)
timeFrame: Up to 24 weeks after infusion
measure: Overall survival (OS)
timeFrame: Up to 24 weeks after infusion
measure: Progression-free survival (PFS)
timeFrame: Up to 24 weeks after infusion
Other outcomes:
Locations:
city: Kunming
country: China
facility: Kunming Hope of Health Hospital
state: Yunnan
Study officials:
affiliation: Kunming Hope of Health Hospital
name: Li Li, MD
role: PRINCIPAL_INVESTIGATOR
References: