A Study of KQ-2003 CAR-T Cell Therapy for Patients With Relapsed or Refractory POEMS Syndrome

Официальное название

A Phase 1 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, and Pharmacokinetic Characterization of KQ-2003 for Patients With Relapsed/Refractory POEMS Syndrome

Обзор

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

Подробное описание

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.

Вмешательства

• Биопрепарат KQ-2003 CAR T-cells
  KQ-2003 CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting both human B cell maturation antigen (anti-BCMA CAR) and CD19 antigen molecules (anti-CD19 CAR) simultaneously as a cellular therapy.

Первичные конечные точки

• Number of patients with dose-limiting toxicity (DLT) [Срок оценки: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy]
• Adverse Event [Срок оценки: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)]
• Maximum Tolerated Dose (MTD) [Срок оценки: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy]
• Recommended Phase 2 Dose (RP2D) [Срок оценки: Through study completion, an average of 1 year]

Вторичные конечные точки (12)

• Response of serum vascular endothelial growth factor level(VEGF) [Срок оценки: Through study completion, an average of 2 years]
• Hematologic response [Срок оценки: Through study completion, an average of 2 years]
• Response of positron emission tomography-scan (PET-CT) [Срок оценки: Through study completion, an average of 2 years]
• Response rate of critical organs [Срок оценки: Through study completion, an average of 2 years]
• Complete response rate (CRR) [Срок оценки: Through study completion, an average of 2 years]
• Disease-free survival (DFS) [Срок оценки: Through study completion, an average of 2 years]
• Overall survival (OS) [Срок оценки: Through study completion, an average of 2 years]
• Maximum concentration (Cmax) [Срок оценки: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)]
• Time to maximum plasma concentration (Tmax) [Срок оценки: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)]
• Levels of IL-2 [Срок оценки: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)]
• Levels of IL-6 [Срок оценки: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)]
• Levels of IL-10 [Срок оценки: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Chinese Academy of Medical Sciences & Peking Union Medical College Hospital — Пекин

Идентификаторы

NCT: NCT06518876 · KQ-2003-BC101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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