Multiple myeloma patients MedDRA version: 21.1 Level: LLT Classification code 10067095 Term: Multiple myeloma progression System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Kyprolis
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Carfilsomib
CAS Number: 868540-17-4
Other descriptive name: CARFILZOMIB
Concentration unit: mg milligram
Sponsors
Helsinki University Central Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients at the age of 18 to below 75 years with the life expectancy of at least three months. 2. Prior confirmed diagnosis of multiple myeloma and measurable disease in blood or urine with at least one of the following: Serum M-protein = 5g/l, Urine M-protein = 200 mg/24 hours, In subjects without detectable serum or urine M-component, serum free light chain (S-FLC) > 100 ml/l (involved light chain) and an abnormal serum kappa/lambda ratio 3. Relapse or progression after 1 to 3 prior treatment lines, which have included proteasome inhibitors (PI, bortezomib and/or ixazomib) and/or lenalidomide. Refractoriness to PI´s and/or lenalidomide is allowed in the preceding cycle. Patients must be carfilzomib naíve. Patients with previous autologous transplantation can be included. 4. Need of treatment of relapse or progression: IMWG criteria for relapse/progression (paraprotein or CRAB criteria or both). (Appendix 5) 5. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care. 6. Females of childbearing potential (FCBP) must have a confirmed negative serum pregnancy test within the 7 days prior to inclusion 7. Females of childbearing potential must use one effective method of contraception and their partners condom during the study and for 120 days following the last study drug treatment dose and male subjects who are sexually active with FCBP must agree to use condom during the study and for 180 days following the last study drug treatment dose. 8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2, or Karnofsky at least 60. (Appendix 1) 9. Patients must meet the following adequate organ and bone marrow function within 21 days prior to inclusion: • Absolute neutrophil count (ANC) 1,000/mm3 (= 1.0 x 109/L) and platelet count 75 x 109/L. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. Granulocyte growth factors are allowed to meet the inclusion criteria? • Hemoglobin (Hb) = 80 g/l (use of erythropoietin and red blood cell transfusions allowed by institutional guidelines, however the most recent RBC may not have given within 7 days prior to obtaining screening Hb • Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Female patients who are lactating or have a positive serum pregnancy test during the screening period. 2. Major surgery within 28 days before enrollment. 3. Radiotherapy within 14 days before enrollment, but if the involved field is small, 7 days will be considered a sufficient interval before onset of the treatment. 4. Glucocorticoid therapy within the 14 days prior to inclusion that exceeds a cumulative dose of 160 mg dexamethasone or 1000 mg prednisone. 5. Central nervous system involvement. 6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. 7. Active congestive heart failure (NYHA III-IV) (Appendix 3), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease or myocardial infarction within 6 months prior to enrollment or left ventricular ejection fraction (LVEF) <40% within one month before randomization. 8. Ongoing or active systemic infection, active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positivity. 9. Any other serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol. 10. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) or to any of the study medications, their analogues, or excipients in the various formulations of any agent. 11. Contraindication to dexamethasone or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment. 12. Diagnosed or treated for another malignancy within 5 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 13. Patient has = Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination within the 14 days prior to inclusion. 14. Participation in another interventional study within the 28 days before this study inclusion. 15. Patients that have been previously treated with elotuzumab or carfilzomib. 16. Primary plasma cell leukemia, systemic AL amyloidosis, Waldenström macroglobulinemia, rare IgM multiple myeloma, POEMS syndrome, myelodysplasia 17. Allogeneic or autologous stem cell transplantation planned 18. Participants receiving any other investigational agents or received within 60 days 19. Pleural effusions requiring thoracocentesis within the 14 days prior the inclusion. 20. Ascites requiring ascitespunction within the 14 days prior to inclusion. 21. Previous allogeneic transplantation 22. Uncontrolled hypertension or uncontrolled diabetes despite medication 23. Known hepatic cirrhosis 24. Severe autoimmune disease 25. Positive direct antiglobulin test (DAT), Coombs test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and feasibility of carfilzomib + elotuzumab + dexamethasone combination and initial efficacy in relapsed or progressed multiple myeloma patients.;Secondary Objective: Not applicable;Primary end point(s): Overall response rate (ORR) with carfilzomib + elotuzumab + dexamethasone;Timepoint(s) of evaluation of this end point: Primary endpoint (ORR) together with the relevant secondary endpoints will be assessed after the minimum follow-up of one year has been reached with the last included patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Complete response rate (CR) • Quality of response (proportion of minimal residual disease (MRD) negativity in patients with at least VGPR response) • Duration of responses • Progression-free survival (PFS) • Time to next treatment (TTNT) • Safety (Adverse events);Timepoint(s) of evaluation of this end point: Primary endpoint (ORR) together with the relevant secondary endpoints will be assessed after the minimum follow-up of one year has been reached with the last included patient. To assess PFS and TTNT all patients will be followed until 4 years after first dose. | — |
Countries
Finland, Sweden
Contacts
Public ContactRaija Silvennoinen
Helsinki University Central Hospital
Outcome results
None listed