Clinical trial NCT06518876: A Study of KQ-2003 CAR-T Cell Therapy for Patients With Relapsed or Refractory POEMS Syndrome
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, and Pharmacokinetic Characterization of KQ-2003 for Patients With Relapsed/Refractory POEMS Syndrome
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: POEMS Syndrome
Lead sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-07-24
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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

Detailed description: 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

Primary outcomes:
measure: Number of patients with dose-limiting toxicity (DLT)
timeFrame: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
measure: Adverse Event
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Maximum Tolerated Dose (MTD)
timeFrame: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Response of serum vascular endothelial growth factor level(VEGF)
timeFrame: Through study completion, an average of 2 years
measure: Hematologic response
timeFrame: Through study completion, an average of 2 years
measure: Response of positron emission tomography-scan (PET-CT)
timeFrame: Through study completion, an average of 2 years
measure: Response rate of critical organs
timeFrame: Through study completion, an average of 2 years
measure: Complete response rate (CRR)
timeFrame: Through study completion, an average of 2 years
measure: Disease-free survival (DFS)
timeFrame: Through study completion, an average of 2 years
measure: Overall survival (OS)
timeFrame: Through study completion, an average of 2 years
measure: Maximum concentration (Cmax)
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Time to maximum plasma concentration (Tmax)
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of IL-2
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of IL-6
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of IL-10
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of TNF-α
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of IFN-γ
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of C-reactive protein (CRP)
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of ferritin
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: CD19+B lymphocyte count
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: CD20+B lymphocyte count
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: CD3+T lymphocyte count
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: CD4+T lymphocyte count
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: CD8+T lymphocyte count
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: ADA
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences & Peking Union Medical College Hospital
Study officials:
References: