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

NCT03155100 | Completed Phase 2 DMC

• 2 other identifiers: NMSG#24/152016-001178-13
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 8

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).

Conditions

Multiple Myeloma in Relapse

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  The proportion of patients having achieved at least partial response.

  3 years

Secondary Outcomes (1)

• Severe adverse events

  3 years

Study Arms (1)

Carfilzomib, elotuzumab, dexamethasone

EXPERIMENTAL

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)

Drug: Carfilzomib for Inj 60 milligram (MG); Drug: Elotuzumab 400 MG; Drug: Dexamethasone

Interventions

Carfilzomib for Inj 60 milligram (MG) DRUG

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

Also known as: Proteasome inhibitor

Carfilzomib, elotuzumab, dexamethasone

Elotuzumab 400 MG DRUG

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

Also known as: Monoclonal antibody

Carfilzomib, elotuzumab, dexamethasone

Dexamethasone DRUG

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

Also known as: Steroid

Carfilzomib, elotuzumab, dexamethasone

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients at the age of 18 to below 75 years with the life expectancy of at least three months.
• 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
• 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.
• 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)
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2, or Karnofsky at least 60.
• 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)
• Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements.

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 28 days before enrollment.
• 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.
• Central nervous system involvement.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
• 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.
• Ongoing or active systemic infection, active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positivity.
• 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.
• 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.
• 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.
• 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.
• Patients refractory to carfilzomib or elotuzumab.
• Primary plasma cell leukemia, systemic AL amyloidosis, Waldenström macroglobulinemia, rare Immunoglobulin M (IgM) multiple myeloma, POEMS syndrome, myelodysplasia
• Allogeneic or autologous stem cell transplantation planned
• Participants receiving any other investigational agents or received within 60 days

Sponsors & Collaborators

• Raija Silvennoinen: lead
• Amgen: collaborator
• Bristol-Myers Squibb: collaborator
• Hospital District of Helsinki and Uusimaa: collaborator

Study Sites (8)

Helsinki University Central Hospital

Helsinki, Finland

Location

Central Finland Central Hospital

Jyväskylä, Finland

Location

Kymenlaakso Central Hospital

Kotka, Finland

Location

Kuopio University Hospital

Kuopio, Finland

Location

Oulu University Hospital

Oulu, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

Turku University Hospital

Turku, Finland

Location

Karolinska University Hospital

Stockholm, Sweden

Location

MeSH Terms

Interventions

carfilzomib; Proteasome Inhibitors; elotuzumab; Antibodies, Monoclonal; Dexamethasone; Steroids

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Raija Silvennoinen, MD, PhD

  Helsinki University Central Hospital CCC Hematology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 14, 2017
• First Posted: May 16, 2017
• Study Start: August 7, 2017
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); FI (7)