A Study of KQ-2003 CAR-T Cell Therapy for Patients With Relapsed or Refractory POEMS Syndrome
NCT Number: NCT06518876
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: POEMS Syndrome
Interventions: BIOLOGICAL: KQ-2003 CAR T-cells
Sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 21
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-31
Completion Date: 2027-12-31
Locations: Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing, 100730, China

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

Primary Outcome Measures: Number of patients with dose-limiting toxicity (DLT), For DLT evaluation, severity (grade) is classified according to common terminology criteria for adverse events version 5.0 (CTCAE v5.0)., Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy|Adverse Event, Safety will be assessed by adverse events (AEs), which include clinically significant abnormalities identified during a medical test (e.g. laboratory tests, electrocardiogram, vital signs, physical examinations). AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) and their severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)., Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Maximum Tolerated Dose (MTD), At least 6 subjects in the MTD dose group must complete the DLT assessment., Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy|Recommended Phase 2 Dose (RP2D), To determine after all subjects in the Phase 1 dose-escalation study completed DLT observation, Through study completion, an average of 1 year
Secondary Outcome Measures: Response of serum vascular endothelial growth factor level(VEGF), The improvements of serum VEGF will be assessed every three months by evaluating changes from baseline and will be described descriptively., Through study completion, an average of 2 years|Hematologic response, Hematologic response is also a criterion for assessing the efficacy of treatment for POEMS syndrome. The improvements of serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) will be assessed every three months by evaluating changes from baseline and will be described descriptively., Through study completion, an average of 2 years|Response of positron emission tomography-scan (PET-CT), Observe the change in FDG uptake in the lesions of the subjects compared to the baseline, assessed every three months., Through study completion, an average of 2 years|Response rate of critical organs, Evaluate the changes in clinical symptoms compared to the baseline according to CTCAE 5.0. The assessment of clinical efficacy is conducted every three months after KQ-2003 CAR T-cells transfusion therapy., Through study completion, an average of 2 years|Complete response rate (CRR), The definition of CRR is the proportion of subjects achieving CR confirmed by efficacy re-assessment after a minimum interval of three months., Through study completion, an average of 2 years|Disease-free survival (DFS), DFS refers to time from treatment until the recurrence of disease (or death) after undergoing the study treatment., Through study completion, an average of 2 years|Overall survival (OS), OS is the time from the start of cell infusion to the death of the subject., Through study completion, an average of 2 years|Maximum concentration (Cmax), Blood and bone marrow samples will be collected and used for pharmacokinetics assessments., Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Time to maximum plasma concentration (Tmax), Blood and bone marrow samples will be collected and used for pharmacokinetics, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Levels of IL-2, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about cytokine levels, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Levels of IL-6, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about cytokine levels, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Levels of IL-10, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about cytokine levels, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Levels of TNF-α, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about cytokine levels, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Levels of IFN-γ, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about cytokine levels, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Levels of C-reactive protein (CRP), Blood samples will be collected and used for pharmacodynamic to evaluate the levels, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|Levels of ferritin, Blood samples will be collected and used for pharmacodynamic to evaluate the levels, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|CD19+B lymphocyte count, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about peripheral blood lymphocyte subsets, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|CD20+B lymphocyte count, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about peripheral blood lymphocyte subsets, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|CD3+T lymphocyte count, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about peripheral blood lymphocyte subsets, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|CD4+T lymphocyte count, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about peripheral blood lymphocyte subsets, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|CD8+T lymphocyte count, Blood samples will be collected and used for pharmacodynamic to evaluate the levels about peripheral blood lymphocyte subsets, Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)|ADA, The trial will evaluate the positive rate, titer and duration or persistence of ADA following the administration of CAR T-Cells., Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)