LENALIDOMIDE for Multiple myeloma | Newly diagnosed multiple myeloma

Inclusion criteria

• {"criterion_text":"- 1. Adult patients of age ≥ 18 and ≤ 70 years at the time of signing the informed consent form\n- 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.\n- 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.\n- 12. Male subjects must ▪ Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a FCBP.  Understand the potential teratogenic risk if the subject donates semen or sperm.  Practice complete abstinence (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g. calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) or agree to use a condom during sexual contact with a pregnant female or a FCBP while taking lenalidomide, carfilzomib and elotuzumab, during any dose interruptions and for 28 days after the last dose of lenalidomide and for 90 days after last dose of carfilzomib if allocated in Arm B without administration of elotuzumab, or for a total of 180 days after last application of elotuzumab, if allocated in Arm A with application of elotuzumab, even if he has undergone a successful vasectomy.  Notify the investigator immediately, if pregnancy or a positive pregnancy test does occur in the partner of a male subject while taking lenalidomide, carfilzomib, and/or elotuzumab.  Not donate semen or sperm while receiving lenalidomide, during dose interruptions and for at least 28 days after the last dose of lenalidomide and for at least 90 days after the last dose of carfilzomib.  Receive counseling about pregnancy precautions and the potential risks of fetal exposure to lenalidomide at a minimum of every 28 days during induction and consolidation phase. In maintenance phase counseling must be conducted with each lenalidomide prescription issued by the investigator.\n- 13. All subjects must ▪ Not donate blood while taking lenalidomide, during dose interruptions and for at least 28 days after the last dose of lenalidomide. ▪ Agree never to give lenalidomide to another person. ▪ Agree to return all unused lenalidomide capsules to the investigator (with exception of prescribed lenalidomide capsules) ▪ During induction and consolidation phase, be aware that no more than a 28-day lenalidomide supply may be dispensed with each cycle of lenalidomide. ▪ During maintenance therapy, be aware that for females of childbearing potential no more than a 28-day lenalidomide supply may be prescribed with each cycle of lenalidomide, for all others no more than a 12 week lenalidomide supply may be prescribed.\n- 2. Eligible for autologous stem cell transplantation (ASCT)\n- 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)\n- 4. Newly diagnosed multiple myeloma according to the IMWG updated criteria42: Clonal bone marrow plasma cells ≥ 10% or extramedullary plasmacytoma 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 < 40 mL per min or serum creatinine > 177 μmol/L (> 2 mg/dL) - Anaemia: haemoglobin value of >2 g/dL below the lower limit of normal, or a haemoglobin value < 10 g/dL - Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or PET-CT ▪ Any one or more of the following markers of malignancy: - Clonal bone marrow plasma cell percentage ≥ 60% - Involved: uninvolved serum free light chain ratio ≥ 100, provided the absolute level of the involved light chain is at least 100 mg/L - One or more focal lesions of at least 5mm or greater in size on MRI studies\n- 5. Measurable disease parameters as follows: ▪ Serum monoclonal paraprotein (M-component) level ≥ 1 g/dL and/or urine Mprotein level ≥ 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\n- 6. ECOG Performance Status ≤ 2\n- 7. Echocardiography with left ventricular ejection fraction (LVEF) ≥ 50%\n- 8. Laboratory test results within these ranges: ▪ White blood cell count (WBC)  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, see Appendix 19.5) ≥ 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)\n- 9. Patient’s legal capacity to consent to study participation"}

Exclusion criteria

• {"criterion_text":"- 1. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)\n- 10. Greater or equal to Grade 2 peripheral neuropathy on clinical examination within 14 days before enrolment\n- 11. Major surgery within 4 weeks prior to randomization\n- 12. Any systemic anti-myeloma therapy except a cumulative dose of 320 mg of dexamethasone\n- 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\n- 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\n- 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\n- 2. Waldenström’s macroglobulinemia or IgM myeloma\n- 3. Plasma cell leukemia (> 2.0 x 109 /L circulating plasma cells by standard differential blood count)\n- 4. Pregnant, breast-feeding females, FCBPs and males who are unwilling to comply with the lenalidomide Pregnancy Prevention Risk Management Plan (see Appendix E).\n- 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\n- 6. Prior cerebral vascular accident (CVA) with persistent neurological deficit\n- 7. Active infection\n- 8. Known HIV-seropositivity, active or chronic hepatitis A, B, C or D-infection (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 in case of patients who tested positive for acute or chronic hepatitis B.\n- 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."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Response assessed per IMWG criteria; MRD negativity assessed by flow cytometry following six cycles of induction treatment."}
• {"endpoint_text":"- For the maintenance phase: 3-year PFS rate calculated from randomization","definition_or_measurement_approach":"Progression-free survival rate at 3 years calculated from date of randomization."}

Secondary endpoints

• {"endpoint_text":"- 1. Objective response rate (ORR) following induction and consolidation treatment with EKRd versus KRd (response evaluation according to IMWG criteria, refer to Appendix A)","definition_or_measurement_approach":"ORR evaluated according to IMWG criteria after induction and consolidation."}
• {"endpoint_text":"- 2. ORR at the end of study treatment programme following induction, ASCT, consolidation, and maintenance treatment (response evaluation according to IMWG criteria, refer to Appendix A; target population: Intent - to - Treat)","definition_or_measurement_approach":"ORR at end of entire treatment programme assessed per IMWG in the Intent-to-Treat population."}
• {"endpoint_text":"- 3. PFS, defined as the time from randomization to the date of disease progression after firstline therapy (study treatment) or death from any cause","definition_or_measurement_approach":"PFS measured as time from randomization to disease progression after first-line therapy or death from any cause."}
• {"endpoint_text":"- 4. 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","definition_or_measurement_approach":"PFS2 measured from randomization to progression or death during/after second-line therapy in ITT population."}
• {"endpoint_text":"- 5. PFS and OS in correlation with cytogenetic abnormalities","definition_or_measurement_approach":"PFS and overall survival analysed by cytogenetic subgroups."}
• {"endpoint_text":"- 6. Improvement of MRD negativity rate as assessed by flow-cytometry following consolidation treatment","definition_or_measurement_approach":"MRD negativity assessed by flow cytometry after consolidation; improvement measured as change in MRD-negative rate."}
• {"endpoint_text":"- 7. Improvement of MRD negativity rate as assessed by flow-cytometry during maintenance treatment","definition_or_measurement_approach":"MRD negativity assessed by flow cytometry during maintenance; improvement measured as change in MRD-negative rate."}
• {"endpoint_text":"- 8. Disease-free survival (DFS) for patients who obtain MRD negativity as assessed by flowcytometry (at any time point)","definition_or_measurement_approach":"DFS measured for patients achieving MRD negativity at any time point."}
• {"endpoint_text":"- 9. OS","definition_or_measurement_approach":"Overall survival measured from randomization to death from any cause."}
• {"endpoint_text":"- 10. OS for patients who obtain MRD negativity as assessed by flow-cytometry (at any time point)","definition_or_measurement_approach":"OS analysed in subgroup of patients who achieved MRD negativity."}
• {"endpoint_text":"- 11. QoL evaluated with EORTC-QLQ C30 and EORTC multiple myeloma module QLQ-MY20","definition_or_measurement_approach":"Quality of life assessments using EORTC QLQ-C30 and QLQ-MY20 instruments."}
• {"endpoint_text":"- 12. Type, incidence, relatedness, and severity of adverse events according to NCI CTCAE version 4.03","definition_or_measurement_approach":"Safety assessed by recording AEs graded per NCI CTCAE v4.03."}
• {"endpoint_text":"- 13. Occurrence of laboratory abnormalities","definition_or_measurement_approach":"Occurrence and incidence of clinically relevant laboratory abnormalities monitored and reported."}

Austria

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

325

Number Of Sites

8

Number Of Participants

82

Germany

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

587

Number Of Participants

492

Primary sponsor

Full Name

Universitaetsklinikum Wuerzburg AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Contract research organisations

Name

Viedoc Technologies AB

Responsibilities

[{"id":985455,"code":"3"},{"id":985456,"code":"6"},{"id":985457,"code":"7"}]

Name

SCRATCH Pharmacovigilance GmbH & Co. KG

Responsibilities

[{"id":985453,"code":"8"}]

Third parties

• {"country":"Germany","full_name":"Meike Maneth","duties_or_roles":"[{\"id\":985458,\"code\":\"1\"}]","organisation_type":"SME"}
• {"country":"Germany","full_name":"Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR","duties_or_roles":"[{\"id\":985454,\"code\":\"14\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Austria","full_name":"Arbeitsgemeinschaft Medikamentoese Tumortherapie gGmbH","duties_or_roles":"[{\"id\":985461,\"code\":\"1\"},{\"id\":985462,\"code\":\"12\"},{\"id\":985463,\"code\":\"5\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"SCRATCH Pharmacovigilance GmbH & Co. KG","duties_or_roles":"[{\"id\":985453,\"code\":\"8\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Universitaetsklinikum Ulm AöR","duties_or_roles":"[{\"id\":985460,\"code\":\"15\",\"value\":\"Diagnostik Molekularzytogenetik\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Schleswig-Holstein AöR","duties_or_roles":"[{\"id\":985459,\"code\":\"15\",\"value\":\"Diagnostik Durchflusszytometrie / Next Generation Sequencing\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"[{\"id\":985455,\"code\":\"3\"},{\"id\":985456,\"code\":\"6\"},{\"id\":985457,\"code\":\"7\"}]","organisation_type":"Non-Pharmaceutical company"}