POEMS Syndrome
Conditions
Keywords
POEMS syndrome, Carfilzomib
Brief summary
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
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
Sponsors
Shanghai Changzheng Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall hematological response rate | 2 years | 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). |
| Overall VEGF response rate | 2 years | 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. |
| Overall neurological response rate | 2 years | Neurological response rate: Neurologic improvement assessed by neurophysiologic examination, modified Rankin Scale, or Overall Neuropathy Limitations Scale (ONLS). 1. Complete response: 0 point; 2. Improvement: Improved by 1 point; 3. Progression: Worsened by 1 point |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the incidence of adverse events and severe adverse events | 2 years | Major Adverse Events 1. Hematologic toxicity: neutropenia, thrombocytopenia, etc. 2. Infections: bacterial pneumonia, sepsis, etc. 3. Worsening of neuropathy 4. Capillary leak syndrome 5. 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 |
| the 2-year overall survival rate | 2 years | 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). |
| Two-year progression-free survival | 2 years | 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) |
Countries
China
Contacts
CONTACTHaiyan He, Dr.
CONTACTXuerou Yu
PRINCIPAL_INVESTIGATORHaiyan He, Dr.
Shanghai Changzheng Hospital
Outcome results
None listed