LENALIDOMIDE for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Patients with newly diagnosed multiple myeloma that need to initiate treatment in accordance with that published in 2014 by the IMWG\n- Left ventricle ejection fraction ≥ 40%.\n- Male patients that receive lenalidomide must agree to use condoms each time they have sexual relations with a pregnant woman or a woman able to become pregnant during the time they are taking the study drug, even if said male patients have undergone a successful vasectomy. If not, they must agree to practice total abstinence (if this is part of the patient’s choice of or normal lifestyle). This commitment must be maintained including during periods when administration of the investigational drug is interrupted and for at least 30 days after treatment has ended. In addition, male patients that receive treatment with lenalidomide must agree not to donate semen or sperm during treatment with the study drug, including during periods of dose interruptions, for at least 90 days after the end of treatment. NOTE: Keeping in mind the age of patients that will be included in this clinical trial (between 65 and 80, inclusive), there is no possibility that women of childbearing potential will be participating. For this reason the pregnancy prevention program (appendix 12) has been modified as a result.\n- Aged between 65 and 80 years old, inclusive.\n- Patient in good overall health, assessed by the health status scale (Geriatric Assessment in Hematology GHA scale, appendix 11). (0-94 points GAH scale) [2]. Patients with a score of ≤42 will be included.\n- Signed informed consent\n- Patients must have measurable disease, defined as: a. For secretory multiple myeloma, measurable disease is defined as the presence of quantifiable M-protein ≥0.5 g/dl, or excretion of free light chains in urine 200 mg/24h or greater. b. For oligo-secretory or non-secretory multiple myeloma, the level of involved plasma free light chains must be ≥10 mg/dl (≥100 mg/L, with an abnormal ratio of free light chains).\n- Functional status ≤2 as defined by Eastern Cooperative Oncology Group (ECOG) (see appendix 6).\n- Life expectancy greater than 3 months.\n- Adequate organ function: a. Platelet count ≥ 50,000/mm3, hemoglobin ≥ 8 g/dl and absolute neutrophil count ≥ 1,000/mm3. The lowest values will be permitted only if they are due to BM infiltration. b. Aspartate transaminase (AST) and alanine aminotransferase ≤ 2.5 times above the upper limit of normal. c. Total bilirubin: ≤ 2 time above the upper limit of normal. d. Serum creatinine ≤ 2 mg/dl. e. Calcium ≤14mg/dl or corrected plasma calcium ≤14mg/dl in patients whose albumin levels are out of range (see appendix 9).\n- In their judgement, the investigator feels that the patient is able to comply with all of the protocol requirements."}

Exclusion criteria

• {"criterion_text":"- Patients older than 81 or younger than 65.\n- Uncontrolled endocrine disease (for example diabetes mellitus, hypo- or hyperthyroidism). These diseases have required relevant changes in medication in the last month or have required hospitalization of the patient in the last 3 months.\n- Patients with ≥ Grade 2 peripheral neuropathy in the 14 days prior to inclusion in the study.\n- Known hypersensitivity to any of the study drugs or their excipients.\n- Patients treated with any other study drug in the 30 days prior to inclusion.\n- Patients with diffuse infiltrative lung disease and/or pericardial effusion.\n- Patients that are unable or unwilling to undergo anti-thrombotic therapy.\n- Patients with severe chronic obstructive pulmonary disease (CPOD) or asthma with forced expiratory volume in the first minute (VEF1) less than 50%.\n- Patients who are not in good general health according to the GAH scale (appendix 11) (>43 points on the GAH scale).\n- Patients who have previously received anti-myeloma treatment, with the exception of steroid pulses in the event of emergency, administration of bisphosphonates or analgesic radiotherapy, or due to the presence of plasmacytomas that caused an emergency.\n- Male patients who do not commit to using a condom during sexual relations with pregnant women or women of childbearing potential, even if said male patients have undergone as successful vasectomy. If not, the must agree to practice total abstinence (if this is part of the patient’s choice of or normal lifestyle).\n- Left ventricle ejection fraction ≥ 40%.\n- Previous medical history of disease other than multiple myeloma (except basal or squamous cell carcinoma, cervical or breast carcinoma in situ, unless the patient has been disease-free for ≥ 5 years.\n- Other relevant diseases or adverse medical conditions: a. Myocardial infarction in the 6 months prior to enrolment in the trial. b. Functional class III-IV s per the NYHA, heart failure, uncontrolled angina, uncontrolled ventricular arrhythmia or acute ischemia detected by electrocardiogram or conduction system anomalies. c. History of significant neurological or psychiatric diseases. d. Active infection. e. Significant non-malignant liver disease (for example cirrhosis, active chronic hepatitis). f. Uncontrolled arterial hypertension. g. Any serious medical condition or psychiatric disorder that might interfere with the patient's understanding of the informed consent form.\n- Positive for Human Immunodeficiency Virus (HIV) or hepatitis B surface antigen, or active hepatitis C virus infection.\n- Limitation in the patient’s capacity to comply with the treatment or follow-up protocol."}

Primary endpoints

• {"endpoint_text":"- The difference between each experimental arm and the control group in terms of immunphenotypic complete response (MRD negative by cytometry) after 18 cycles of induction therapy. Evaluation will be carried out using next generation flow cytometry through a study developed by the EuroFlow Consortium in accordance with response guidelines recently proposed by the IMWG [3].","definition_or_measurement_approach":"Immunophenotypic complete response defined as MRD negativity by next generation flow cytometry (NGF) using the EuroFlow Consortium assay according to IMWG response guidelines; measured after 18 cycles of induction therapy."}

Secondary endpoints

• {"endpoint_text":"- Difference between each experimental arm and the control group in terms of the probability of Progression Free Survival from the date of randomization until progression or death, midway through induction (9 cycles) at the end of induction (18 cycles), post-consolidation, and yearly during maintenance. As well, differences in terms of of probability of SLP2, TTP, OS and proportions of standard response (stringent CR, CR, VGPR and PR).","definition_or_measurement_approach":"Progression Free Survival (PFS) from randomization to progression or death at specified timepoints (mid-induction 9 cycles, end induction 18 cycles, post-consolidation, yearly during maintenance). Also SLP2, TTP, OS and standard response categories compared between arms."}
• {"endpoint_text":"- Kinetics of MRD elimination after: a. 9 cycles (midway through induction). b. 18 cycles (end of induction, primary endpoint). c. post-consolidation d. yearly during maintenance therapy, for at least five years.","definition_or_measurement_approach":"MRD measured by NGF at defined timepoints (after 9 cycles, after 18 cycles, post-consolidation, and annually during maintenance up to 5 years) to evaluate elimination kinetics."}
• {"endpoint_text":"- The evaluation of MRD using NGF will allow us to evaluate: a. 3.a The difference between each experimental group and the control group in terms of proportion of immunphenotypic complete response (MRD negativity by cytometry) after 9 cycles of induction therapy.","definition_or_measurement_approach":"Proportion MRD-negative by NGF after 9 cycles compared between experimental and control arms."}
• {"endpoint_text":"- The evaluation of MRD using NGF will allow us to evaluate: 3.b Reduction in MRD levels in patients treated in the control group, as well as in patients who receive KRd without daratumumab between the end of induction therapy and the end of consolidation therapy In addition, the difference in the levels of MRD between the two above-mentioned arms at the end of short consolidation therapy (22 months) and the KRd+ daratumumab arm at the end of a prolonged period of induction therapy (18 months).","definition_or_measurement_approach":"Change in MRD levels (NGF) between end of induction and end of consolidation; comparison of MRD levels between arms at end of consolidation and at end of prolonged induction as specified."}
• {"endpoint_text":"- The evaluation of MRD using NGF will allow us to evaluate:3 .c Difference, evaluated yearly after the start of maintenance therapy, in preservation of response obtained after consolidation in both patients with negative MRD and those with positive MRD.","definition_or_measurement_approach":"Annual assessment during maintenance of preservation of response post-consolidation, stratified by MRD status, using NGF."}
• {"endpoint_text":"- Correlation of classic efficacy/survival criteria with immunphenotypic response: a. Standard response categories: Stringent CR, CR, VGPR, PR b. Time from randomization to second disease progression or the moment when the third line of treatment is initiated. SLP2. c. Overall Survival","definition_or_measurement_approach":"Correlation analyses between immunophenotypic MRD/response and standard response categories, time to second progression (SLP2) and overall survival."}
• {"endpoint_text":"- Difference in the quality of life scores in the questionnaires EQ-5D/5L, QLQ-C30 and MY20 between initiation and months 6, 12, and 18 during induction therapy, after consolidation, and every 6 months during maintenance.","definition_or_measurement_approach":"QoL measured using EQ-5D/5L, QLQ-C30 and MY20 at baseline, months 6, 12, 18, post-consolidation and every 6 months during maintenance; differences between arms will be compared."}
• {"endpoint_text":"- Counts and proportions of treatment-related adverse effects for each treatment arm and in each treatment phase.","definition_or_measurement_approach":"Safety assessed as counts and proportions of treatment-related adverse events by arm and treatment phase (induction/consolidation/maintenance)."}

Spain

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

02-05-2025

Processing Time Days

197

Number Of Sites

56

Number Of Participants

462

Primary sponsor

Full Name

Fundacion PETHEMA

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Hospital Universitario 12 De Octubre","duties_or_roles":"[4]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Universidad De Navarra","duties_or_roles":"[4]","organisation_type":"Educational Institution"}
• {"country":"Spain","full_name":"Evidenze Health Espana S.L.","duties_or_roles":"[1,5]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Hospital Universitario De Salamanca","duties_or_roles":"[4]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Farmavenix S.A.","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}