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

NCT06518876 | Not Yet Recruiting Phase 1

• 1 other identifier: KQ-2003-BC101
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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

Conditions

POEMS Syndrome

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (22)

• Response of serum vascular endothelial growth factor level(VEGF)

  Through study completion, an average of 2 years

• Hematologic response

  Through study completion, an average of 2 years

• Response of positron emission tomography-scan (PET-CT)

  Through study completion, an average of 2 years

• Response rate of critical organs

  Through study completion, an average of 2 years

• Complete response rate (CRR)

  Through study completion, an average of 2 years

Study Arms (4)

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

Biological: KQ-2003 CAR T-cells

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

Biological: KQ-2003 CAR T-cells

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

Biological: KQ-2003 CAR T-cells

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.

Biological: KQ-2003 CAR T-cells

Interventions

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.

Phase 1a: High dose group; Phase 1a: Low dose group; Phase 1a: Medium dose group; Phase 1b: RP2D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Novatim Immune Therapeutics (Zhejiang) Co., Ltd.: lead

Study Sites (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital

Beijing, 100730, China

Location

MeSH Terms

Conditions

POEMS Syndrome

Condition Hierarchy (Ancestors)

Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Jian Li, M.D.

CONTACT

010-65296114; lijian@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 24, 2024
• Study Start: August 31, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 24, 2024

Record last verified: 2024-07

Locations

CN (1)