LENALIDOMIDE for Multiple myeloma

Stratification factors

• Frailty score (3 levels)
• Cytogenetic FISH results (2 levels)

Inclusion criteria

• {"criterion_text":"-Patients has given voluntary written informed consent before the performance of any study related procedure\n-1.2.1) Clonal bone marrow plasma cell percentage ≥60% (clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used)\n-1.2.2) Involved/uninvolved serum free light chain ratio ≥100 (values based on the serum Freelite assay. The involved free light chain must be ≥100 mg/L)\n-1.2.3) >1 focal lesion detected by MRI (magnetic resonance imaging) studies (each focal lesion must be 5 mm or more in size\n-According to physician’s opinion, patients can undergo either one of the two standard treatments and procedures\n-Females of childbearing potential (FBCP) must use an effective contraceptive method for 28 days before the study treatment, during the treatment and for at least 3 months after the last dose of study drugs\n-Male subjects must use an effective barrier method if sexually active with FCBP during treatment and for at least 6 months after the last dose of study drug\n-Patients should be ineligible for ASCT, defined as: - ≥ 65 years old; - younger than 65 years but who reject the transplant procedure or with abnormal cardiac, pulmonary, hepatic and renal function defined as: • LVEF (left ventricular ejection fraction) < 40%; • FEV1 (forced expiratory volume-1 second) < 40%; •\tBilirubin > 1.5 UNL, AST/ALT >2.5 UNL; • Creatinine clearance < 60 mL/min.\n-Patients with newly diagnosed symptomatic multiple myeloma (NDMM) based on standard IMWG (International Myeloma Working Group) criteria:\n-1) Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB features and myeloma-defining events:\n-1.1) Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically\n-1.1.1) Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL)\n-1.1.2) Renal insufficiency: creatinine clearance (CLcr)<40 mL per minute (measured or estimated by validated equations) or serum creatinine > 177 µmol/L (>2mg/dL)\n-1.1.3) Anemia: hemoglobin value of >20g/L below the lower limit of normal, or a hemoglobin value <100g/L\n-1.1.4) Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has <10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement\n-1.2) Any one or more of the following biomarkers of malignancy:"}

Exclusion criteria

• {"criterion_text":"-Hypersensitivity to any active substance or to any of the excipients (lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, boron, mannitol, nitrogen, crospovidone, colloidal anhydrous silica, hypromellose, titanium dioxide, macrogol, talc, sodium starch glycolate, sodium benzoate, propylene glycol, sodium dihydrogen phosphate, hydroxypropyl beta cyclodextrin, sodium saccharin, sodium EDTA, sodium hydroxide, L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 20, sorbitol (E420), recombinant human hyaluronidase (rHuPH20))\n-Administration of prophylactic vaccine from 8 to 2 weeks before starting treatment\n-Hereditary intolerance to fructose\n-Pregnant and lactating women\n-FBCP that do not follow the Pregnancy Prevention Plan requirements\n-Acute diffuse infiltrative pulmonary and pericardial disease\n-Acute viral infections (e.g. herpes simplex or ocular herpes simplex, herpes zoster, varicella)\n-Systemic mycotic or bacterial infections, unless specific anti-infectious therapy is ongoing\n-Peptic ulcer\n-Psychosis"}

Primary endpoints

• {"endpoint_text":"-PFS will be measured from the date of randomization to the date of first observation of PD, or death from any cause as an event. Subjects who withdraw from the study will be censored at the time of the last complete disease assessment. Subjects who complete the study, have not progressed, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to FU will also be censored at the time of last contact.","definition_or_measurement_approach":"Progression-free survival (PFS) measured from randomization to first observed disease progression (PD) or death from any cause; censoring rules: withdraws, study-complete non-progressors at cut-off, and lost to follow-up censored at last assessment/contact."}

Secondary endpoints

• {"endpoint_text":"-The rate of MRD negativity at 6 months after the start of treatment is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level) at 6 months using ITT principle. For patients who withdraw from the study or are lost to follow up before these timepoints, the best MRD assessment will be considered.","definition_or_measurement_approach":"MRD negativity assessed at 6 months using Next Generation Flow with ≥10^-5 sensitivity; analysis by ITT; for early withdrawers or lost to follow-up the best MRD assessment is used."}
• {"endpoint_text":"-The rate of MRD negativity is determined as the proportion of patients with MRD negativity by Next Generation Flow (≥10-5 sensitivity level) at 6, 12, 24-, 36-, 48- and 60-months using ITT principle. For patients who withdraw from the study or are lost to follow up before 6, 12, 24, 36, 48 and 60 months, the best MRD assessment will be considered. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment.","definition_or_measurement_approach":"MRD negativity assessed by Next Generation Flow at specified timepoints (6,12,24,36,48,60 months) at ≥10^-5 sensitivity; ITT principle; classification rules for missing assessments defined."}
• {"endpoint_text":"-ORR will include complete response (CR) and partial response (PR) using the International Response Criteria reported by Durie et al. Categories of response will include stringent CR (sCR), CR, very good partial response (VGPR), PR and PD. If, during the course of the study, other relevant categories are identified in literature, such new categories may be added. Responders are defined as subjects with at least a PR.","definition_or_measurement_approach":"Overall response rate (ORR) includes sCR, CR, VGPR, PR by International Response Criteria; responders defined as ≥ PR."}
• {"endpoint_text":"-DOR is defined as time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.","definition_or_measurement_approach":"Duration of response (DOR): time from first documented response to disease progression; censoring for lost to follow-up, death due to other causes, or study end."}
• {"endpoint_text":"-PFS2 is defined as the time from randomization to objective tumor progression on next-line treatment or death from any cause.","definition_or_measurement_approach":"PFS2: time from randomization to progression on next-line therapy or death from any cause."}
• {"endpoint_text":"-OS is defined as the time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death. Subjects who withdraw consent will be censored at the time of withdrawal. Subjects who complete the study and are still alive at the cut-off date of final analysis will be censored at the cut-off date. Subjects lost to FU will also be censored at the time of last contact.","definition_or_measurement_approach":"Overall survival (OS): time from randomization to death; censoring rules provided for withdrawal, completion alive at cut-off, lost to follow-up."}
• {"endpoint_text":"-TNT will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event. Subjects who withdraw consent will be censored at the time of the last complete disease assessment. Subjects who complete the study and are still alive at the cut-off date of final analysis will be censored at the cut-off date. Subjects lost to FU will also be censored at the time of last contact.","definition_or_measurement_approach":"Time to next therapy (TNT): from randomization to start of next anti-myeloma therapy; death before therapy considered an event; censoring rules defined."}
• {"endpoint_text":"-TTP will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD. Subjects who withdraw from the study or die from causes other than PD will be censored at the time of the last complete disease assessment. Subjects who complete the study, have not progressed, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. Subjects lost to FU will also be censored at the time of last contact.","definition_or_measurement_approach":"Time to progression (TTP): time from randomization to first observation of progression or PD-related death; censoring for other causes of death, withdrawal, completion, lost to follow-up."}
• {"endpoint_text":"-Safety will be evaluated by assessing the incidence, severity and type of AEs according to NCI-CTCAE v. 4.0. and the incidence of toxicities as well as the rate of treatment discontinuation or death for toxicity will be evaluated during the entire duration of the trial.","definition_or_measurement_approach":"Safety endpoints: incidence, severity, type of adverse events using NCI-CTCAE v4.0; evaluate toxicity incidence, treatment discontinuation, and death due to toxicity across trial duration."}
• {"endpoint_text":"-Validation of frailty score will be made by estimating efficacy and safety endpoints in patients stratified according to Myeloma Frailty Score and by considering patients’ non-Myeloma polydrug therapies.","definition_or_measurement_approach":"Validate frailty score by comparing efficacy and safety outcomes in subgroups stratified by Myeloma Frailty Score, accounting for concomitant therapies."}
• {"endpoint_text":"-QoL will be evaluated through Health-Related QoL (HRQoL) questionnaires: EORTC-QLQ-C30 (a generic, multidimensional, cancer-specific QoL questionnaire), QLQ-MY20 (a specific 20- item MM module) and EQ-5D-5L (a generic assessment of five health categories and overall health score). After baseline visit, questionnaires should be collected every 3 months for the first year and every 6 months thereafter.","definition_or_measurement_approach":"Quality of life assessed by EORTC-QLQ-C30, QLQ-MY20, and EQ-5D-5L at baseline, every 3 months in year 1, then every 6 months."}
• {"endpoint_text":"-Health-related costs will be reported through questionnaires. Every 3 months for the first year and every 6 months thereafter, patients or care-givers will be asked to fill out self-reported questionnaire regarding outpatient and GPs visits, emergency care, in-patient stays, home care, nursing home or residential care, care-giving, and personal use and expenditure for health related services.","definition_or_measurement_approach":"Health-related costs captured via patient/caregiver questionnaires at scheduled intervals (q3 months year1, q6 months thereafter) covering healthcare utilization and expenditures."}
• {"endpoint_text":"-Infectious risk complications will be evaluated in terms of incidence, severity, type of infection, need for hospitalization, deferral or suspension of study treatment with possible impact on PFS.","definition_or_measurement_approach":"Infectious complications measured by incidence, severity, infection type, hospitalization requirement, and impact on treatment (deferral/suspension) and PFS."}

Italy

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

05-12-2025

Processing Time Days

501

Number Of Sites

32

Number Of Participants

450

Primary sponsor

Full Name

Universita' Degli Studi Di Torino

Organisation Type

Educational Institution

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Italy","full_name":"Mipharm S.p.A.","duties_or_roles":"code 15: Label supplier","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Universita' Degli Studi Di Torino","duties_or_roles":"code 4","organisation_type":"Educational Institution"}
• {"country":"Italy","full_name":"IRCCS Centro Di Riferimento Oncologico Della Basilicata","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Italy","full_name":"Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Italy","full_name":"Azienda Ospedaliero Universitaria Parma","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}