An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cell Injections for the Treatment of Refractory Primary Immune Thrombocytopenia
A single arm, open-label pilot study is designed to determine the safety and effectiveness of CD19 CAR NK cells (KN5501) in patients with refractory immune thrombocytopenia. 9 patients are planned to be enrolled in the dose-escalation trial (9×10\^9 cells, 13.5×10\^9 cells). The primary objective of the study is to evaluation of the safety and feasibility of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The secondary objective is to evaluate evaluation of KN5501 for the treatment of refractory immune thrombocytopenia. The exploratory objective is to evaluate expansion, persistence and ability to deplete CD19 positive B cells of KN5501 in patients with refractory immune thrombocytopenia.
• Age: ≥ 18 years old and ≤ 65 years old, male or female, subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF);
• Diagnosis of immune thrombocytopenia (UTP) (according to American Society of Hematology 2019 guidelines and International ITP Working Group);
• Platelet count is decreased in routine blood tests at least two consecutive times, with no obvious abnormalities in the morphology of blood cells on microscopic examination of peripheral blood smears;
• Spleen is not enlarged during screening;
• The morphology of bone marrow cells in subjects is characterized by increased or normal megakaryocytes with impaired maturation;
• Exclude other secondary thrombocytopenia: secondary thrombocytopenia due to autoimmune diseases, thyroid disorders, lymphoproliferative disorders, myelodysplastic syndromes (MDS), aplastic anemia (AA), various malignant blood disorders, neoplastic infiltrates, chronic liver disease, hypersplenism, common variable immunodeficiency disease (CVID), infections, vaccinations, etc.; thrombocytopenia; drug-induced thrombocytopenia; homozygous thrombocytopenia; thrombocytopenia during pregnancy; congenital thrombocytopenia and pseudothrombocytopenia. Thrombocytopenia due to consumption; drug-induced thrombocytopenia; isoimmune thrombocytopenia; thrombocytopenia in pregnancy; congenital thrombocytopenia and pseudothrombocytopenia;
• Subjects with refractory ITP who are refractory to first-line therapeutic agents, thrombopoietic agents in second-line therapy, and rituximab, or who have had ineffective splenectomies/postoperative recurrences, and who undergo diagnostic reassessment and remain diagnosed with ITP;
• Patients with refractory ITP: refractory to first-line therapeutic agents, thrombopoietic agents in second-line therapy, and rituximab; patients diagnosed with ITP despite unsuccessful splenectomy/postoperative recurrence on diagnostic reassessment
• ECOG score ≤ 1;
⁃ Left ventricular ejection fraction (LVEF) ≥50% and no clinically significant pericardial effusion;
⁃ ≥ 4 weeks after subjects received last dose treatment (Radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments);
⁃ NRT, antimalarial monotherapy, antimalarials in combination with OCS and/or immunosuppressants, combination of OCS and/or immunosuppressants.