Newly Diagnosed Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Revlimid
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Current Sponsor code: Lenalidomide
Concentration unit: mg milligram(s)
Concentration t
Sponsors
University Hospital Wuerzburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be enrolled in this study only if they meet all of the following inclusion criteria and none of the exclusion criteria below: 1. Adult patients of age = 18 and = 70 years at the time of signing the informed consent form 2. Eligible for autologous stem cell transplantation (ASCT) 3. Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma (only dexamethasone at a cumulative dose of 320 mg; plasmapheresis/dialysis without concomitant chemotherapy, local irradiation of bone lesions; and surgical intervention permitted as pretreatment) 4. Newly diagnosed multiple myeloma according to the IMWG updated criteria: Clonal bone marrow plasma cells = 10% or biopsy proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: • Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: - Hypercalcaemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL) - Renal insufficiency: creatinine clearance 177 µmol/L (> 2 mg/dL) - Anaemia: haemoglobin value of > 2 g/dL below the lower limit of normal, or a haemoglobin value 200 mg/24 hours or • In case of IgA myeloma: Serum monoclonal paraprotein level = 0.5 g/dL and/or urine M-protein level = 200 mg/24 hours or • For patients with no detectable M-component: Serum FLC assay: Involved FLC level = 10 mg/dL (= 100 mg/L) provided serum FLC ratio is abnormal 6. ECOG Performance Status = 2 7. Echocardiography with left ventricular ejection fraction (LVEF) = 50% 8. Laboratory test results within these ranges: • White blood cell count = 2 x 109/L • Absolute neutrophil (ANC) count = 1.0 x 109/L • Platelet count = 75 x 109/L • Haemoglobin > 8 g/dL • Calculated creatinine clearance (estimation of the glomerular filtration rate [GFR]; according to MDRD) = 30 mL/minute • Total bilirubin = 1.5 x upper limit of normal (ULN) • AST and ALT = 2.5 x ULN • Corrected serum calcium level < 3.5 mmol/L (< 14 mg/dL) 9. Patient’s legal capacity to consent to study participation 10. Patients capable to understand the purposes and risks of the study, who are willing and able to participate in the study and from whom written and dated informed consent to participate in the study has been obtained. 11.All females ? Must acknowledge to have understood the hazards lenalidomide can cause to an unborn fetus and the necessary precautions associated with the use of lenalidomide. • The investigator must ensure that a FCBP: - Complies with the conditions of the pregnancy prevention plan, including confirmation that she has an adequate level of understanding. - Acknowledges the aforementioned requirements. 12. Male subjects must ? Understand the potential teratogenic risk if engaged in sexual activity with a pregna
Exclusion criteria
Exclusion criteria: 1. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Waldenström’s macroglobulinemia or IgM myeloma 3. Plasma cell leukemia (> 2.0 x 109/L circulating plasma cells by standard differential blood count) 4. Pregnant, breast-feeding females, FCBPs and males who are unwilling to comply with the lenalidomide Pregnancy Prevention Risk Management Plan. 5. Patients with high cardiovascular risk, including but not limited to history of myocardial infarction or coronary stenting in the past 6 months; NYHA Class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, severe uncontrolled arrhythmias 6. Prior cerebral vascular accident (CVA) with persistent neurological deficit 7. Active infection 8. Known HIV-seropositivity, active or chronic hepatitis A, B, C or Dinfection (including patients who are tested anti-HBC positive and/or HBsAg positive) –serological testing for hepatitis A; B; C, D required. However, testing for hepatitis D only required for patients who tested positive for active acute or chronic hepatitis B. 9. Any other severe concomitant disease or disorder, including the presence of laboratory abnormalities, which places the subject at unacceptable risk or which could influence patient’s ability to participate in the study and his/her safety during the study or interfere with interpretation of study results 10. Greater or equal to Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment 11. Major surgery within 4 weeks prior to randomization 12. Any systemic anti-myeloma therapy within 4 weeks of randomization except a max. cumulative dose of 320 mg auf dexamethasone. 13. Any prior or concurrent malignancy other than multiple myeloma. Exceptions include patients who have been disease-free for at least five years before study entry or patients with adequately treated and completely resected basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer 14. Known hypersensitivity to carfilzomib, lenalidomide, and elotuzumab or to any of the excipients of carfilzomib, lenalidomide, and elotuzumab or to any other component of any study drug formulation 15. Participation in any other clinical trial or treatment with any experimental drug or other experimental therapy within 28 days before enrolment to the study or during study participation until the end of treatment visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the rate of patients who have VGPR or better response according to IMWG criteria and are MRD negative as assessed by flow cytometry following two different induction regimens (quadruple [E-KRd] vs. triple [KRd]) in newly diagnosed multiple myeloma patients and to determine progression-free survival (PFS) following maintenance treatment.;Secondary Objective: To assess long-term efficacy, quality of life (QoL) and safety of the treatment regimens. To assess the impact of MRD negativity regardless of International Myeloma Working Group (IMWG) response on disease-free survival (DFS) and overall survival (OS).;Primary end point(s): There are two coprimary endpoints: • For the induction phase: Rate of patients who have VGPR or better response according to IMWG criteria and are MRD-negative as assessed by flow cytometry following six cycles of induction treatment • For the maintenance phase: 3-year PFS rate calculated from randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy variables: • Objective response rate (ORR) following induction and consolidation treatment with E-KRd versus KRd (response evaluation according to IMWG criteria) •ORR at the end of study treatment programme with induction, ASCT, consolidation, and maintenance treatment (response evaluation according to IMWG criteria; target population: Intent-to-Treat) • PFS, defined as the time from randomization to the date of disease progression after first-line therapy (study treatment) or death from any cause •PFS 2, defined as the time from randomization to the date of disease progression or death from any cause during/after second-line therapy in the Intent-to-Treat Population •PFS and OS in correlation with cytogenetic abnormalities •Improvement of MRD negativity rate as assessed by flow-cytometry following consolidation treatment •Improvement of MRD negativity rate as assessed by flow-cytometry during maintenance treatment •Disease-free survival (DFS) for patients who obtain MRD negativity as assessed by flow-cytometry (at any time point) •OS •OS for patients who obtain MRD negativity as assessed by flow-cytometry (at any time point) •QoL evaluated with EORTC-QLQ C30 and EORTC multiple myeloma module QLQ-MY20 Safety variables: •Type, incidence, relatedness, and severity of adverse events according to NCI CTCAE version 4.03 •Occurrence of laboratory abnormalities | — |
Countries
Austria, Germany
Contacts
Public ContactStudy Coordinator
University Hospital
Outcome results
None listed