KCD (Carfilzomib/Cyclophosphamide/Dexamethasone) Regimen for the Treatment of Newly Diagnosed POEMS Syndrome

Официальное название

A Single-center, Prospective, Open-label Investigation of the KCD (Carfilzomib/Cyclophosphamide/Dexamethasone) Regimen for the Treatment of Newly Diagnosed POEMS Syndrome

Обзор

This study is a single-center, prospective, open-label clinical study to evaluate the efficacy and safety of KCD(Carfilzomib/Cyclophosphamide/Dexamethasone) regimen in subjects with newly diagnosed POEMS Syndrome.

Подробное описание

POEMS syndrome is a rare plasma cell disorder, with an incidence of approximately 0.3 per 100,000 individuals. Its typical clinical manifestations encompass peripheral neuropathy, organomegaly, endocrine abnormalities, M -proteinemia, and cutaneous alterations, frequently accompanied by papilledema, fluid retention, thrombocytosis, osteosclerosis, and elevated levels of vascular endothelial growth factor (VEGF). Plasma cell clonal proliferation and VEGF overexpression are regarded as the key pathogenic mechanisms of POEMS syndrome. Currently, there is no standardized treatment protocol for POEMS syndrome, and anti-plasma cell therapy remains the primary therapeutic approach. Clinically recommended treatments involve alkylating agents, immunomodulators, proteasome inhibitors, and autologous hematopoietic stem cell transplantation (ASCT). Carfilzomib, a second-eneration proteasome inhibitor, has been extensively utilized in multiple myeloma. The evidence supporting the use of carfilzomib in POEMS syndrome is restricted to case reports and small-scale retrospective studies, and prospective clinical trials evaluating carfilzomib-based regimens as first-line therapy are still lacking. Therefore, this study designed a centralized, prospective, open-label clinical trial to evaluate the KCD regimen(carfilzomib + cyclophosphamide + dexamethasone) in patients with newly-diagnosed POEMS syndrome. This study plans to enroll 20 subjects, all subjects will receive KCD regimen for 6-8 cycles. The primary endpoints include overall hematological response rate, neurological response rate, and vascular endothelial growth factor (VEGF) response rate. Secondary endpoints include hematological and non-hematological toxicities, progression-free survival (PFS), and overall survival (OS).

Вмешательства

• Препарат CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE
  carfilzomib at a dose of 27 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15,cyclophosphamide at a dose of 200 mg/m2 iv on days 1, 8 and 15 and dexamethasone at a dose of 20 mg (10 mg for patients \>75 years) days 1, 2, 8, 9, 15 and 16

Первичные конечные точки

• Overall hematological response rate [Срок оценки: 2 years]
• Overall VEGF response rate [Срок оценки: 2 years]
• Overall neurological response rate [Срок оценки: 2 years]

Вторичные конечные точки (3)

• the incidence of adverse events and severe adverse events [Срок оценки: 2 years]
• the 2-year overall survival rate [Срок оценки: 2 years]
• Two-year progression-free survival [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Newly diagnosed POEMS syndrome meeting the Dispenzieri diagnostic criteria (2023 version);
• Age 18-75 years;
• ECOG performance status 0-3, with an estimated life expectancy >3 months;
• No active infective diseases;
• No prior anti-POEMS therapy except for corticosteroids;
• No severe organic impairment of major organs, meeting the following laboratory requirements: creatinine clearance ≥40 mL/min, total bilirubin ≤1.5 × upper limit of normal (ULN); AST and ALT ≤2.5 × ULN; cardiac enzymes <2 × ULN; left ventricular ejection fraction within normal range on echocardiography, and no clinically significant electrocardiogram abnormalities;
• Absolute neutrophil count ≥1.5 × 10\^9/L without prior growth factor support; platelet count ≥50 × 10\^9/L without platelet transfusion within 7 days prior to screening; hemoglobin ≥60 g/L;
• Ability to swallow and take medication orally;
• Completion of all screening and assessments as outlined in the study protocol;
• Signed informed consent for chemotherapy.

Критерии исключения

• POEMS syndrome complicated by multiple myeloma, light chain amyloidosis, or Waldenström macroglobulinemia;
• HIV positivity, or active hepatitis A, hepatitis B, or hepatitis C infection; or hepatitis B virus DNA >10\^2 copies/mL;
• Concurrent severe unstable medical conditions, including heart failure, renal failure, liver failure, bleeding disorders, arterial/venous thrombotic events within 6 months, uncontrolled diabetes mellitus, or a history of active hemorrhagic cystitis;
• History of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) within the past 2 years that caused end-organ damage or required systemic immunosuppressive or disease-modifying therapy;
• Severe active infections (e.g., untreated tuberculosis, pulmonary aspergillosis);
• Presence of other malignancies (except non-melanoma skin cancer, in situ cervical, bladder, or breast cancer with disease-free survival >5 years);
• Epilepsy requiring medication, dementia, or other mental status abnormalities that interfere with understanding or complying with the study protocol;
• Drug use, medical, psychological, or social conditions that may interfere with study participation or outcome assessment;
• Pregnancy or breastfeeding;
• Any condition deemed by the investigator to make the patient unsuitable for enrollment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Changzheng Hospital — Шанхай

Идентификаторы

NCT: NCT07652879 · CZ-POEMS-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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