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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1a: Low dose group | Experimental | Infusion of KQ-2003 CAR T-cells by single dose of 0.5×10^6 CAR-T cells/kg |
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| Phase 1a: Medium dose group | Experimental | Infusion of KQ-2003 CAR T-cells by single dose of 1.0×10^6 CAR-T cells/kg |
|
| Phase 1a: High dose group | Experimental | Infusion of KQ-2003 CAR T-cells by single dose of 2.0×10^6 CAR-T cells/kg |
|
| Phase 1b: RP2D | Experimental | After all subjects in the Phase 1a dose-escalation study completed DLT observation, RP2D was determined based on the analysis results for the phase 1b expansion study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KQ-2003 CAR T-cells | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jian Li, M.D. | Contact | 010-65296114 | lijian@pumch.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chinese Academy of Medical Sciences & Peking Union Medical College Hospital | Beijing | 100730 | China |
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| ID | Term |
|---|---|
| D016878 | POEMS Syndrome |
| ID | Term |
|---|---|
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
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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) |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |