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

Overview

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.

Interventions

• Biological 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.

Primary outcome measures

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

Secondary outcome measures (12)

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

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

Identifiers

NCT: NCT06518876 · KQ-2003-BC101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗