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

NCT05739227 | Unknown Early Phase 1

• 1 other identifier: XYFY2022-KL252-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Lymphoblastic Leukemia; B-cell Lymphoma; Chronic Lymphocytic Leukemia

Keywords

B-cell hematologic malignancies; allogenic CD19-CAR-NK cells

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities

  Adverse events assessed according to NCI-CTCAE v5.0 criteria

  1 month

• Objective Response Rate(ORR)

  Assessment of ORR (ORR = CR + CRi + PR) at 3 months of treatment

  3 months

Secondary Outcomes (3)

• Progression free survival(PFS)

  Month 6,12

• Overall Survival(OS)

  Month 6, 12, 18 and 24

• Minimal-residual disease negative overall response rate(MRD-ORR)

  Month 6, 12

Study Arms (1)

allogenic CD19-CAR-NK

EXPERIMENTAL

Enrolled patients will receive prespecified dose of allogenic CD19-CAR-NK cells.

Other: allogenic CD19-CAR-NK cells

Interventions

allogenic CD19-CAR-NK cells OTHER

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

allogenic CD19-CAR-NK

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age18-75years old, no gender or race;
• Expected survival period ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
• 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;
• 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;
• 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%;
• Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Central nervous system involved;
• ≥2 grade persistent nonhematologic toxicity of associated with prior treatment;
• 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);
• 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;
• 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;
• History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;
• Previous or next organ transplant(except for HCT);
• Women who are pregnant (urine/blood pregnancy test positive) or lactating;
• Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 6 months after enrollment;
• Any unstable condition potentially imperiling patient safety and compliance;
• Known alcohol dependence or drug dependence;
• According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Sponsors & Collaborators

• Xuzhou Medical University: lead

Study Sites (1)

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kailin Xu, M.D., Ph.D.

  Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kailin Xu, M.D., Ph.D.

CONTACT

15162166166; lihmd@163.com

Junnian Zheng, M.D., Ph.D

CONTACT

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 11, 2023
• First Posted: February 22, 2023
• Study Start: March 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: February 22, 2023

Record last verified: 2023-02

Locations

CN (1)