Safety and Efficacy of Allogenic CD19-CAR-NK Cells in Treatmenting r/r B-cell Hematologic Malignancies

Trial Title: Safety and Efficacy of Allogenic CD19-CAR-NK Cells in Treatmenting r/r B-cell Hematologic Malignancies

NCT ID: NCT05739227

Condition: Acute Lymphoblastic Leukemia
B-cell Lymphoma
Chronic Lymphocytic Leukemia

Conditions: Official terms:
Leukemia
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Hematologic Neoplasms

Conditions: Keywords:
B-cell hematologic malignancies
allogenic CD19-CAR-NK cells

Study type: Interventional

Study phase: Early Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Other
Intervention name: allogenic CD19-CAR-NK cells
Description: The relapsed/refractory B-cell hematologic malignancies patients will receive allogenic CD19-Targeted CAR-NK cells infusion up to 3 dose levels (1x10^6/kg, 5x10^6/kg, 2x10^7/kg) after FCE chemotherapy
Arm group label: allogenic CD19-CAR-NK

Summary: This is an open label, single-arm, Phase I study to evaluate the efficacy and safety of allogenic CD19-CAR-NK cells in subjects with refractory or relapsed B-cell hematologic malignancies. A leukapheresis procedure will be performed to manufacture Anti-CD19 chimeric antigen receptor (CAR) modified NK cells. Prior to allogenic CD19-CAR-NK cells infusion subjects will receive lymphodepleting therapy with fludarabine, cyclophosphamide and etoposide.

Detailed description: This open label, single-arm, Phase I study aims to evaluate the efficacy and safety of allogenic CD19-CAR-NK cells in subjects with refractory or relapsed B-cell hematologic malignancies. A leukapheresis procedure will be performed to manufacture Anti-CD19 chimeric antigen receptor (CAR) modified NK cells. Prior to allogenic CD19-CAR-NK cells infusion subjects will receive lymphodepleting therapy with fludarabine, cyclophosphamide and etoposide. After infusion, the investigators will observe the characteristics of dose limited toxicity (DLT), and determine the maximum tolerable agent MTD and rp2d were confirmed. To provide basis for the dosage and treatment plan of cell products in follow-up clinical trials.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Age18-75years old, no gender or race; 2. Expected survival period ≥ 3 months; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; 4. Confirmed relapsed/refractory B-cell tumor and tumor cells expressing CD19, including acute B-cell lymphoblastic leukemia and B-cell lymphoma; and meets the following criteria for refractory or relapsed B-cell hematologic malignancies: (1) Refractory or relapsed acute B-cell lymphoblastic leukaemia (meets one of the following four criterias): a.Relapse within 6 months after the initial remission; b. Initial refractory patients with failure to achieve complete remission(CR) after 2 cycles of standard chemotherapy; c.Failure to achieve CR or relapse after first line or multiline salvage chemotherapy; d.Patients who are not fitable for hematopoietic stem cell transplantation (HCT), or give up HCT due to limitations, or relapse after HCT.(2) Refractory or relapsed B-cell lymphoma (meets 1 of the following first 4 criterias plus the fifth): a.≤50% decrease in SPD of up to 6 target measurable nodes and extranodal sites or disease progression after 4 cycles of standard chemotherapy; b.Relapse within 6 months after CR; c.Two or more times relapse after CR; d.Subjects who are not fitable for HCT, or give up HCT due to limitations, or relapse after HCT; e.Subjects must be treated with adequate treatment, including at least monoclonal antibodies against CD20 or combination chemotherapy containing anthracyclines; 5. Measurable lesions meets at least one of the following requirements during screening: (1) For lymphoma patients, the length of a single lesion ≥15mm or two or more lesions with the length ≥10mm; (2) Acute B-cell lymphoblastic leukaemia patients with persistent positive MRD or relapse with positive MRD; 6. Within 3 days prior to initial treatment, the organ functions meet the following requirements: (1) complete blood cell count: a.Absolute neutrophil counts ≥ 1.0 ×10^9/L and not treated with G-CSF within 7 days; b.Hemoglobin ≥6g/dL(red blood cell transfusion is permitted); c.Platelet ≥50×10^9/L, (platelet transfusion is permitted);(2) Liver function: alanine transaminase (ALT)/ aspartate aminotransferase(AST) ≤ 3× times upper normal limit(ULN), total bilirubin ≤ 2 times ULN (direct bilirubin ≥1.5 times ULN is acceptable for subjects with Gilbert-Meulengracht syndrome);(3) Coagulation function: International standardized ratio (INR) or activated partial thrombin time (APTT) ≤1.5 times ULN; (4) Renal function: serum creatinine≤1.5×ULN or creatinine clearance rate ≥30mL/min; (5) Corrected serum calcium ≤14mg/dL (≤3.5mmol/L) or free calcium ≥6.5mg/dL(≥1.6mmol/L); (6) Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; 7. Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: 1. Central nervous system involved; 2. ≥2 grade persistent nonhematologic toxicity of associated with prior treatment; 3. Systemic steroid therapy exceeding the equivalent of ≥30mg/kg/day of prednisone within 48 hours prior to the first dose of study drug or other immunosuppressive therapies(except for topical and inhaled glucocorticoid therapy, or short-term prophylactic therapy with glucocorticoid); 4. Severe cardiovascular and cerebrovascular diseases, including: (1) Some cardiovascular and cerebrovascular diseases (such as congestive heart failure, acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism, etc.) occurr within 6 months prior to the first dose of study drug; (2)New York Heart Association (NYHA) Class ≥3 or uncontrolled malignant arrhythmias; (3)The researchers assessed that the subjects with other cardiovascular and cerebrovascular diseases are not suitable for the study; 5. Any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: HBV, HCV, HIV, syphilis infection, or active pulmonary tuberculosis; 6. History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines; 7. Previous or next organ transplant(except for HCT); 8. Women who are pregnant (urine/blood pregnancy test positive) or lactating; 9. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 6 months after enrollment; 10. Any unstable condition potentially imperiling patient safety and compliance; 11. Known alcohol dependence or drug dependence; 12. According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: The Affiliated Hospital of Xuzhou Medical University

Address:
City: Xuzhou
Zip: 221000
Country: China

Status: Recruiting

Contact:
Last name: Kailin Xu, M.D.,Ph.D.

Phone: 15162166166
Email: lihmd@163.com

Start date: March 1, 2023

Completion date: May 2025

Lead sponsor:
Agency: Xuzhou Medical University
Agency class: Other

Source: Xuzhou Medical University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05739227