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

Phase 1Not Yet RecruitingNCT06518876

Novatim Immune Therapeutics (Zhejiang) Co., Ltd.21 enrolled

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

POEMS Syndrome

Interventions

KQ-2003 CAR T-cellsBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital

Beijing, China

Outcomes

Primary Outcomes

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).

Time frame: 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).

Time frame: 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.

Time frame: 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

Time frame: Through study completion, an average of 1 year

Secondary Outcomes

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.

Time frame: 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.

Central Contacts

Jian Li, M.D.

CONTACT

010-65296114 lijian@pumch.cn

Data from ClinicalTrials.gov

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