Study to evaluate the efficacy of 3 different treatments, followed by maintenance treatment, in older adult patients, between 65 and 80 years old, in good general health and newly diagnosed multiple myeloma.

Trial details

Who runs it

Fundacion PETHEMA

Trial code

EU 2024-516905-22-00

Record updated

2026. október 26.

Original description

Compare the efficacy in terms of immunphenotypic complete response at 18 months of the standard treatment in Spain for patients with newly diagnosed multiple myeloma that are ineligible for bone marrow transplant (VMP followed by Rd) with experimental KRd treatment (carfilzomib, lenalidomide, dexamethasone, alone or in combination with daratumumab) as induction therapy for 18 cycles in a selected patient population in good general health with newly diagnosed multiple myeloma.Read full original descriptionShow less

Induction therapy with bortezomib, melphalan and prednisone (VMP) followed by lenalidomide and dexamethasone (Rd) vs. carfilzomib, lenalidomide and dexamethasone (KRd) with/without daratumumab, 18 cycles, followed by consolidation and maintenance with lenalidomide and daratumumab: a phase III, multicenter, randomized clinical trial for older adult patients between 65 and 80 years old, in good general health with newly-diagnosed multiple myeloma

Compare the efficacy in terms of immunphenotypic complete response at 18 months of the standard treatment in Spain for patients with newly diagnosed multiple myeloma that are ineligible for bone marrow transplant (VMP followed by Rd) with experimental KRd treatment (carfilzomib, lenalidomide, dexamethasone, alone or in combination with daratumumab) as induction therapy for 18 cycles in a selected patient population in good general health with newly diagnosed multiple myeloma.

Inclusion: Patients with newly diagnosed multiple myeloma that need to initiate treatment in accordance with that published in 2014 by the IMWG; Left ventricle ejection fraction ≥ 40%; 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; Aged between 65 and 80 years old, inclusive; 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; Signed informed consent; 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); Functional status ≤2 as defined by Eastern Cooperative Oncology Group (ECOG) (see appendix 6); Life expectancy greater than 3 months; 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); In their judgement, the investigator feels that the patient is able to comply with all of the protocol requirements.

Exclusion: Patients with ≥ Grade 2 peripheral neuropathy in the 14 days prior to inclusion in the study; Patients treated with any other study drug in the 30 days prior to inclusion; Patients that are unable or unwilling to undergo anti-thrombotic therapy; 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; 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; 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; Known hypersensitivity to any of the study drugs or their excipients; Patients with diffuse infiltrative lung disease and/or pericardial effusion; Patients with severe chronic obstructive pulmonary disease (CPOD) or asthma with forced expiratory volume in the first minute (VEF1) less than 50%; Positive for Human Immunodeficiency Virus (HIV) or hepatitis B surface antigen, or active hepatitis C virus infection; Left ventricle ejection fraction ≥ 40%; Patients older than 81 or younger than 65; 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; Patients who are not in good general health according to the GAH scale (appendix 11) (>43 points on the GAH scale); 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); Limitation in the patient’s capacity to comply with the treatment or follow-up protocol.

EU CTIS 2024-516905-22-00