Short summary

New and more effective drugs and their combinations are needed to improve the overall survival of relapsed or progressive multiple myeloma patients. The current study aim to determine the treatment effects of Carfilzomib, Elotuzumab and Dexamethasone combination on patient reported outcomes (PROs) in relapsed or progressed multiple myeloma patients. 

Rationale

Multiple myeloma is the most common hematological malignancy after lymphomas and is considered as an incurable disease. The overall survival though has doubled in the last three decades from a median of 2-3 years to 4-6 years in elderly patients, and up to 8-10 years for younger patients. The vast majority of patients experience relapse or progression of the disease sooner or later after first-line therapy. Treatment of relapse and progression is challenging and has significant impact on the overall survival. Therefore, new and more effective drugs and their combinations are needed. The primary objective of the present phase II trial is to investigate the safety and feasibility of 2^nd generation Carfilzomib, Elotuzumab and Dexamethasone combination and initial efficacy with relapsed or progressed multiple myeloma patients using overall response rate as primary endpoint. Secondary objectives are to determine the effects of Carfilzomib, Elotuzumab and Dexamethasone on health-related PROs during treatment in the current trial. The PROs cover scales on physical function, symptoms and global health besides disease-specific multiple myeloma questions.  

Description of the cohort

40 multiple myeloma patients with a life expectancy of at least three months, age between 18 and 75 years, who have relapsed or progressed after 1 to 3 prior treatment lines. Patients are included from hematological departments at university hospitals in Finland (Helsinki, Turku, Tampere, Kuopio, Oulo, Kymenlaakson, Keski-Suomen) and Sweden (Karolinska). All centers are part of the Nordic Myeloma Study Group (NMSG). 

Data and biological material

Treatment schedule:

Carfilzomib, Elotuzumab and Dexamethasone combination is administrated in 28 days treatment cycles as follows: Cycles 1-2: Carfilzomib and Elotuzumab are administered at weekly intervals on cycle days 1, 8 and 15. Dexamethasone will be given on days 1, 8, 15 and 22. Cycles 3-8: Carfilzomib and Dexamethasone administered similarly to cycles 1-2. Elotuzumab administered on cycle days 1 and 15. Cycles 9 and until withdrawal from the study: Carfilzomib, Elotuzumab and Dexamethasone are administered repeatedly at day 1 and 15 in a 28 day cycle and continued until relapse or progression or excess toxicity.

Data from the PROs European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and the EORTC Multiple Myeloma Module (QLQ-MY20) are collected at day 1 (baseline) and day 15 in cycle 1-8, at day 1cycle 9 and all of the following cycles until withdraw from the study equal to relapse or progression or excess toxicity.

Collaborating researchers and departments

Helsinki University Hospital Hematology, Finland  

• Sponsor, Raija Silvennoinen, MD, PhD

Turku University Hospital, Department of Hematology, Finland

• Mervi Putkonen, MD

Tampere University Hospital, Department of Hematology, Finland

• Marja Sankelo, MD

Kuopio University Hospital, Department of Hematology, Finland

• Esa Jantunen, MD

Oulo University Hospital, Department of Hematology, Finland

• Marjaana Säily, MD

Kymenlaakso Central Hospital, Department of Hematology, Finland

• Anu Räsänen, MD

Keski-Suomen Central Hospital, Department of Hematology, Finland

• Anu Sikiö, MD

Karolinska University Hospital, Department of Haematology, Sweden

• Hareth Nani, MD., PhD., Professor