a study of kq-2003 car-t cell therapy for patients with relapsed or refractory poems syndrome

Conditions: POEMS Syndrome

Summary: this is a multicenter, open-label, dose-escalation/expansion phase 1 study to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic characteristics and determine the recommended dose of kq-2003 car t-cells for patients with relapsed/refractory poems syndrome

the study included the phase 1a dose escalation study and the phase 1b cohort extension study. the phase 1a study is an open, dose-escalation design with 3 dose groups according to the "3+3" dose escalation rule: low dose group (0.5×10\^6 car t cells/kg), medium dose group (1.0×10\^6 car t cells/kg), high dose group (2.0×10\^6 car t cells/kg). after initial confirmation of maximum tolerated dose (mtd) or recommended phase 2 dose (rp2d), a phase 1b cohort extension study will be conducted.

Eligibility criteria:
inclusion criteria: * age ≥18 years old, male or female; * diagnosis of poems syndrome with relapsed or refractory disease; * eastern cooperative oncology group (ecog) performance ≤2 ; * adequate venous access for the apheresis of peripheral blood mononuclear cell; * vascular endothelial growth factor (vegf) ≥1200ng/l； * overall neuropathy limitations scale (onls) ≥ 1; * adequate organ function; * able and willing to comply with the study protocol and follow-up plan, and sign the informed consent form in writing. exclusion criteria: * subjects who had previously received bcma-cd19 dual-target car-t cell products or autologous stem cell transplantation within 12 weeks before the collection of peripheral blood mononuclear cells; * known allergy or hypersensitivity reactions to cyclophosphamide, fludarabine, dimethyl sulfoxide (dmso), cd19, or bcma-targeted drugs; * received any treatment that might influence the activity of car-t cells prior to the collection of peripheral blood mononuclear cells; * have history of vaccination within the 4 weeks preceding the collection of peripheral blood mononuclear cells; * have tested positive for cytomegalovirus and/or mycobacterium tuberculosis, or had any uncontrolled active infection within 14 days prior to the collection of peripheral blood mononuclear cells; * subjects infected with active hbv or hcv, hiv, syphilis; * subjects with known central nervous system disease, for example, seizure disorders, clinically significant cerebral ischemia/hemorrhage, dementia); * subjects currently experiencing active autoimmune diseases; diagnosed with immunodeficiency or receiving any other form of immunosuppressive therapy within 7 days prior to enrollment in this study; * subjects with active bleeding or vte events (such as pulmonary embolism or deep vein thrombosis) require anticoagulation; * have following severe diseases: unstable angina, cerebrovascular accident or transient ischemic attack, myocardial infarction , new york heart association (nyha) class ≥ iii, congestive heart failure, poorly controlled severe arrhythmias or other cardiac diseases requiring mechanical support; subjects with known chronic obstructive pulmonary disease (copd) with a forced expiratory volume in 1 second (fev1) \< 50% of predicted normal; subjects with known moderate or severe persistent asthma, or a history of asthma within the past 2 years, or currently having any category of uncontrolled asthma; subjects requiring oxygen to maintain adequate oxygen saturation; subjects with hypertension whose blood pressure cannot be lowered to the following range despite treatment with two or more antihypertensive medications; * have active malignancies; * have any non-hematologic toxicity resulting from prior treatments that cannot be restored to ≤ grade 1 or baseline, excluding alopecia and grade 2 neuropathy; * subjects had participated in other clinical trials and used its investigational drugs within the 3 months prior to the collection of peripheral blood mononuclear cells; * history of alcohol abuse, drug addiction, substance abuse, or mental illness within the past year; * pregnant or lactating women; * any situation that the investigator believes may increase the risk of subjects or interfere with the results of clinical trials