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

Official title

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

Overview

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.

Detailed description

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).

Interventions

• Drug 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

Primary outcome measures

• Overall hematological response rate [Time frame: 2 years]
• Overall VEGF response rate [Time frame: 2 years]
• Overall neurological response rate [Time frame: 2 years]

Secondary outcome measures (3)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Changzheng Hospital — Shanghai

Identifiers

NCT: NCT07652879 · CZ-POEMS-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗