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

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

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.

Study Overview

• Status: Recruiting
• Conditions: POEMS Syndrome
• Intervention / Treatment: Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE

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).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haiyan He, Dr.; Phone Number: +86 13661513012; Email: doctorhehaiyan@126.com
• Study Contact Backup: Name: Xuerou Yu

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Changzheng Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed POEMS syndrome meeting the Dispenzieri diagnostic criteria (2023 version);
2. Age 18-75 years;
3. ECOG performance status 0-3, with an estimated life expectancy >3 months;
4. No active infective diseases;
5. No prior anti-POEMS therapy except for corticosteroids;
6. 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;
7. 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;
8. Ability to swallow and take medication orally;
9. Completion of all screening and assessments as outlined in the study protocol;
10. Signed informed consent for chemotherapy.

Exclusion Criteria:

1. POEMS syndrome complicated by multiple myeloma, light chain amyloidosis, or Waldenström macroglobulinemia;
2. HIV positivity, or active hepatitis A, hepatitis B, or hepatitis C infection; or hepatitis B virus DNA >10^2 copies/mL;
3. 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;
4. 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;
5. Severe active infections (e.g., untreated tuberculosis, pulmonary aspergillosis);
6. Presence of other malignancies (except non-melanoma skin cancer, in situ cervical, bladder, or breast cancer with disease-free survival >5 years);
7. Epilepsy requiring medication, dementia, or other mental status abnormalities that interfere with understanding or complying with the study protocol;
8. Drug use, medical, psychological, or social conditions that may interfere with study participation or outcome assessment;
9. Pregnancy or breastfeeding;
10. Any condition deemed by the investigator to make the patient unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: carfilzomib, cyclophosphamide and 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 in 28 days cycles	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; Other Names: KCD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall hematological response rate	hematological response rate: Complete Remission (CR_H): Normal bone marrow; negative serum and urine immunofixation electrophoresis; disappearance of M-protein.; Very Good Partial Remission (VGPR_H): Reduction of M-protein by >90% (baseline M-protein ≥5 g/L).; Partial Remission (PR_H): Reduction of M-protein by ≥50% (baseline M-protein ≥10 g/L).; No Response (NR_H): Failure to meet criteria for PR_H.; Progressive Disease (PD): Reappearance of M-protein in serum and/or urine, or an increase of >25% from the lowest level (with absolute M-protein increase ≥5 g/L).	2 years
Overall VEGF response rate	VEGF response rate: Complete Remission (CR_V): Normalization of serum VEGF (elevation typically defined as serum VEGF >2 times the upper limit of normal).; Partial Remission (PR_V): Reduction of VEGF by ≥50%.; No Response (NR_V): Failure to meet criteria for PR_V.; Progressive Disease (PD): Persistent (≥2 consecutive measurements) elevation of VEGF , or persistent elevation of VEGF by 50% from the post-treatment nadir.	2 years
Overall neurological response rate	Neurological response rate: Neurologic improvement assessed by neurophysiologic examination, modified Rankin Scale, or Overall Neuropathy Limitations Scale (ONLS).; Complete response: 0 point;; Improvement: Improved by 1 point;; Progression: Worsened by 1 point	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of adverse events and severe adverse events	Major Adverse Events; Hematologic toxicity: neutropenia, thrombocytopenia, etc.; Infections: bacterial pneumonia, sepsis, etc.; Worsening of neuropathy; Capillary leak syndrome; Thrombotic events Grading and Definition of Serious Adverse Event All adverse events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Gr	2 years
the 2-year overall survival rate	Two-year overall survival (2-year OS) is defined as the proportion of patients who remain alive at two years following the start of treatment (or from the date of diagnosis).	2 years
Two-year progression-free survival	Two-year progression-free survival (2-year PFS) is defined as the proportion of patients who remain alive and have not experienced disease progression at two years following the start of treatment (or from the time of diagnosis)	2 years

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Investigators: Principal Investigator: Haiyan He, Dr., Shanghai Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: POEMS syndrome, Carfilzomib
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Hematologic Diseases; Immunoproliferative Disorders; Congenital Abnormalities; Abnormalities, Multiple; Paraproteinemias; Blood Protein Disorders; Polyneuropathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; POEMS Syndrome; Organic Chemicals; Hydrocarbons; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Dexamethasone; Cyclophosphamide; carfilzomib
• Other Study ID Numbers: CZ-POEMS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: POEMS syndrome is a rare disease, and its clinical data are highly valuable

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No