Carfilzomib + Elotuzumab + Dexamethasone for Relapsed Multiple Myeloma After 1-3 Prior Treatment Lines

NCT ID: NCT03155100

Last Updated: 2023-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-07
• Study Completion Date: 2023-08-31

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.

Conditions

Multiple Myeloma in Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carfilzomib, elotuzumab, dexamethasone

Carfilzomib 70 milligram(mg)/m2 iv (56 mg/m2 for first five patients for cycles 1-2) once weekly, on days 1, 8 and 15 (cycles 1-8), from cycle 9 on days 1 and 15 until progression or toxicity; elotuzumab 10 mg/kg iv on days 1,8,15 for cycles 1-2, on days 1and 15 from cycle 3 until progression or toxicity; dexamethasone 40 mg weekly (shared to po and iv)

Group Type: EXPERIMENTAL

Carfilzomib for Inj 60 milligram (MG)

Intervention Type: DRUG

All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone

Elotuzumab 400 MG

Intervention Type: DRUG

All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone

Dexamethasone

Intervention Type: DRUG

All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone

Interventions

Carfilzomib for Inj 60 milligram (MG)

All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone

Intervention Type: DRUG

Elotuzumab 400 MG

All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone

Intervention Type: DRUG

Dexamethasone

All patients will have similar effective study drug combination; karfilzomib plus elotuzumab plus dexamethasone

Intervention Type: DRUG

Other Intervention Names

Proteasome inhibitor; Monoclonal antibody; Steroid

Eligibility 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 (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:

• 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

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 refractory to carfilzomib or elotuzumab.

16. Primary plasma cell leukemia, systemic AL amyloidosis, Waldenström macroglobulinemia, rare Immunoglobulin M (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 puncture 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Hospital District of Helsinki and Uusimaa

OTHER

Sponsor Role: collaborator

Raija Silvennoinen

OTHER

Sponsor Role: lead

Responsible Party

Raija Silvennoinen

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Raija Silvennoinen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Central Hospital CCC Hematology

Locations

Oulu University Hospital

Oulu, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Hospital

Turku, , Finland

Karolinska University Hospital

Stockholm, , Sweden

Helsinki University Central Hospital

Helsinki, , Finland

Central Finland Central Hospital

Jyväskylä, , Finland

Kymenlaakso Central Hospital

Kotka, , Finland

Kuopio University Hospital

Kuopio, , Finland

Countries

Finland; Sweden

Other Identifiers

2016-001178-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NMSG#24/15

Identifier Type: -

Identifier Source: org_study_id