Multiple Myeloma
Conditions
Interventions
single arm:CKVD ( 28 days/cycle)
Cycle 1 (C1):
Aponermin: 10 mg/kg, Days 1-5
Carfilzomib: 20 mg/m^2 on Days 1-2, 27 mg/m2 on Days 8-9 and 15-16
Venetoclax: 400 mg, Days 1-14
Dexamethasone: 20 mg, intr
Sponsors
Department of Hematology, Beijing Chao-Yang Hospital Capital Medical University
Eligibility
Sex/Gender
All
Age
19 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Age >18 years old. 2. Diagnosed with multiple myeloma (MM) according to the 2014 IMWG diagnostic criteria, with measurable disease at screening, meeting at least one of the following criteria: 1) Serum M protein level >10 g/L; or 2) Urine M protein level >200 mg/24 hours; or 3) Light chain MM without measurable M protein in serum or urine: serum free light chain (FLC) >100 mg/L and an abnormal serum FLC ratio (?/?) (0.26-1.65). 3. Patients with early-line relapsed MM and an expected survival of >= 6 months. 4. Subjects must have received 1-3 prior lines of therapy. Induction therapy and stem cell transplantation (± maintenance) will be considered as one line of therapy. Subjects must have received at least one proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib) and one immunomodulatory agent (e.g., lenalidomide, pomalidomide, excluding thalidomide) and experienced disease progression or relapse after treatment with a regimen containing at least one of these agents (as monotherapy or in combination). Patients may or may not have been exposed to anti-CD38 monoclonal antibodies and must be refractory to bortezomib and/or lenalidomide. Radiation therapy, bisphosphonates, or a single short course of corticosteroids (not exceeding an equivalent dose of dexamethasone 20 mg/day for 4 days) will not be considered as prior lines of therapy. 5. Evidence of disease progression based on IMWG criteria during or after the most recent treatment regimen. Disease progression must meet at least one of the following criteria compared to the lowest value achieved: - Serum M protein increase of 25% (absolute increase >= 5 g/L); or M protein increase of 10 g/L (if baseline serum M protein >= 50 g/L); - Urine M protein increase of 25% (absolute increase >= 200 mg/24 hours); - If serum and urine M protein are undetectable, increase in the difference between involved and uninvolved FLC by 25% (absolute increase >100 mg/L); - If serum and urine M protein and involved FLC are undetectable, increase in bone marrow plasma cell percentage by 25% (absolute increase >= 10%); - Appearance of new extramedullary lesions: increase in SPD of more than one measurable lesion by >= 50% compared to the lowest value, or increase in the long axis of a lesion >= 1 cm by 50%; - If circulating plasma cells are the only measurable lesion, an increase in circulating plasma cells by >50% (at least 200 cells/µL). 6. ECOG performance status of 0-2 at screening and before the start of study treatment. 7. Subjects must meet the following hematological criteria at enrollment: **Hematology:** - Hemoglobin >= 80 g/L, without red blood cell transfusion or erythropoietin use within 7 days prior to laboratory testing. - Platelet count: >75×10^9/L for subjects with bone marrow plasma cells 50×10^9/L for subjects with bone marrow plasma cells >= 50% (without platelet transfusion or thrombopoietin receptor agonist use within 7 days prior to laboratory testing). - Absolute neutrophil count (ANC) >0.5×10^9/L (growth factor use is allowed, but G-CSF or GM-CSF must be discontinued 7 days prior to laboratory testing, and pegylated G-CSF must be discontinued 14 days prior). **Serum biochemistry:** - AST, ALT 30 mL/min, calculated using the MDRD formula or measured by 24-hour urine creatinine clearance; - Total bilirubin <= 2.5×ULN, except for subjects with congenita
Exclusion criteria
Exclusion criteria: Candidates meeting any of the following criteria will be excluded from this study: 1. Contraindications, life-threatening allergies, hypersensitivity reactions, or intolerance to excipients of the study drugs. 2. Patients who have received treatment with Aponermin, carfilzomib, or venetoclax. 3. Receipt of targeted therapy, epigenetic therapy, investigational drugs, or invasive experimental medical devices within 21 days or >5 half-lives (whichever is shorter); administration of investigational vaccines (except for SARS-CoV-2 vaccines) within 4 weeks; administration of live attenuated vaccines within 4 weeks; monoclonal antibody therapy within 21 days; cytotoxic therapy within 21 days; proteasome inhibitor (PI) therapy within 14 days; immunomodulatory drug (IMiD) therapy within 14 days; radiotherapy within 14 days or focal radiotherapy within 7 days. 4. Known active CNS involvement or clinical signs of leptomeningeal involvement by multiple myeloma. If either is suspected, whole-brain MRI and lumbar puncture cytology must be negative. 5. Diagnosed with plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes), or primary light chain amyloidosis at screening. 6. Diagnosed with a non-hematologic malignancy within the past 3 years (unless cured) or therapy-related myelodysplastic syndrome. 7. Presence of the following cardiac conditions: - New York Heart Association (NYHA) Class III or IV congestive heart failure. - Myocardial infarction or coronary artery bypass surgery within 6 months. - Clinically significant ventricular arrhythmias or a history of unexplained syncope. - History of severe non-ischemic cardiomyopathy. 8. Presence of any of the following conditions: - Uncontrolled hepatitis B infection (HBSAg or HBV-DNA positive). If the infection status is unclear, HBV-DNA levels must be measured to confirm the infection status. - Active hepatitis C virus (HCV) infection, defined as a positive HCV-RNA test. Subjects with a history of positive HCV antibodies must undergo HCV-RNA testing. Subjects with a history of chronic HCV infection (defined as both HCV antibodies and HCV-RNA positive) who have completed antiviral treatment and have undetectable HCV-RNA for at least 12 weeks after treatment are eligible. - COPD with FEV1 <50% of the predicted standard value. - Moderate or severe persistent asthma or uncontrolled asthma of any type within the past 2 years. - Significant neuropathy at baseline assessment (Grade 3, Grade 4, or Grade 2 with pain). 9. Major surgery within 2 weeks before the start of study treatment, incomplete recovery from prior surgery, or planned major surgery during the study treatment period or within 2 weeks after the last dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Best complete response (CR) rate after CKVD treatment; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival rate;Respnse rate at least very good partial response(VGPR);NGF-MRD negativity rate;Progression-free survival (PFS);Overall survival(OS);Safty ; | — |
Countries
China
Contacts
Public ContactWen Gao
Beijing Chao-Yang Hospital Capital Medical University
Outcome results
None listed