Multiple Myeloma in Relapse
Conditions
Brief summary
The main aim of this study is to assess the ORR with a new drug combination, carfilzomib (CAR) + elotuzumab (ELO) + dexamethasone (CAR-ELO-Dex).
Detailed description
This Nordic Myeloma Study Group study is a phase 2 study for advanced multiple myeloma (MM) patients below 75 years of age. The main aim of this study is to assess the overall response rate (ORR) with a new drug combination, carfilzomib + elotuzumab + dexamethasone (CAR-ELO-Dex). Even if this is not a randomized study rough comparisons can be done with earlier reports of different regimens in the same clinical situation. In addition, safety assessment is of critical importance for a new regimen. A modern concept is to study the depth of complete responses (CR) with a sensitive multiparameter flow cytometry (MFC) method for minimal residual disease (MRD) assessment - an endpoint that is mostly lacking in previous studies for this patient population. We assume that treatment with this new combination of CAR + ELO + Dex will produce at least as good responses as the most efficient regimens so far used in this clinical situation, and there will be a substantial proportion of CR responses with MRD-negativity which can be regarded as an indicator of high-level treatment efficacy and which gives a good basis for comparisons of treatment efficacy between different study regimens in future. The target population of the study is the patients who have relapsed or progressed after 1 to 3 prior treatment lines in which PI (bortezomib and/or ixazomib) and/or lenalidomide have been included. The primary endpoint is overall response rate while the secondary endpoints include complete remission, duration of response, assessment of the depth (quality) of CR with MRD measurement by flow cytometry, estimation of progression free survival (PFS) and time to next treatment, and evaluation of adverse events and safety.
Interventions
DRUGCarfilzomib for Inj 60 milligram (MG)
All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone
DRUGElotuzumab 400 MG
All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone
DRUGDexamethasone
All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone
Sponsors
Amgen
Bristol-Myers Squibb
Hospital District of Helsinki and Uusimaa
Raija Silvennoinen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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 (bortezomib, carfilzomib and/or ixazomib) and/or lenalidomide. Refractoriness to bortezomib, ixazomib and/or lenalidomide is allowed in the preceding cycle. Patients with previous autologous transplantation can be included. 4. Need of treatment of relapse or progression: IMWG criteria for relapse/progression (paraprotein or hypercalcemia, renal insufficiency, anemia, bone disease (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. 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 red blood cells (RBC) may not have given within 7 days prior to obtaining screening Hb * Total bilirubin \< 1.5 times the upper limit of the normal range (ULN). * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 times the ULN. * Calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault estimation of creatinine clearance (CRcl): CRcl (mL/min) = (140 - age) x (weight \[kg\]) / 72 x (serum creatinine \[mg/dL\]); for females, multiply by 0.85 (Cockcroft 1976, Luke 1990) 10. Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements. 11. Negative pregnancy test at inclusion if applicable
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | 3 years | The proportion of patients having achieved at least partial response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severe adverse events | 3 years | Non-hematological grade 3 or more severe adverse events more or at least 70 percent |
Countries
Finland, Sweden
Outcome results
None listed