A multicenter, open label, randomized phase II study comparing daratumumab combined with bortezomib-cyclophosphamide-dexamethasone (Dara-VCd) versus the association of bortezomib-thalidomide-dexamethasone (VTd) as pre transplant induction and post transplant consolidation, both followed by a maintenance phase with ixazomib alone or in combination with daratumumab, in newly diagnosed multiple myeloma (MM) young patients eligible for autologous stem cell transplantatio

Phase 1

Conditions: YOUNG PATIENTS AFFECTED BY MULTIPLE MYELOMA (MM) TO THE DIAGNOSIS ELIGIBLE TO THE AUTOLOGOUS TRANSMISSION OF STEM CELLS
MedDRA version: 21.0Level: LLTClassification code: 10028228Term: Multiple myeloma Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2024-511781-37-00

Lead Sponsor: European Myeloma Network Stichting

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 332

Inclusion Criteria

Patient at least 18 years of age and = 65 years., Women of childbearing potential must commit to either abstain continuously from heterosexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, hormonal patches, vaginal rings or implants] or partner’s vasectomy through a medical assessment of success of the procedure, according to local procedure) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing and for at least 4 weeks before starting thalidomide through 90 days after the last dose of study drugs and 6 months after the last dose of cyclophosphamide. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy., Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 90 days after the last dose of study drugs and 6 months after the last dose of cyclophosphamide., Patient with an ECOG performance status score of 0, 1, or 2 or Karnofsky performance status = 60%., Pretreatment clinical laboratory values within 30 days of enrolment: - Platelet count =75 x 10^9 /L; - Absolute neutrophil count (ANC) = 1 x 10^9 /L (G-CSF use is permitted); - Corrected serum calcium <14 mg/dL (<3.5 mmol/L); - Aspartate transaminase (AST) = 2.5 x the upper limit of normal (ULN); - Alanine transaminase (ALT) = 2.5 x the ULN; - Total bilirubin = 1.5 x the ULN; - Calculated or measured creatinine clearance = 30 mL/minute, Patient has a life-expectancy >3 months., Patient eligible for ASCT., LVEF = 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available., Newly diagnosed multiple myeloma patient., Patient has given voluntary written informed consent before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care., Patient with documented multiple myeloma and measurable disease as defined by: 1) Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma. 2) Measurable disease as defined by at least one of the following: 2.1) serum M-protein level =1 g/dL or urine M-protein level =200 mg/24 hours; or 2.2) Light chain multiple myeloma: involved serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio., Evidence of end organ damage/presence of biomarkers of malignancies, specifically: 1) 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). 2) Renal insufficiency: creatinine clearance <40 mL per minute (measured or estimated by validated equations) or serum creatinine >177 µmol/L (>2 mg/dL). 3) Anaemia: haemoglobin value of >20 g/L below the lower limit of normal, or haemoglobin value <100 g/L. 4) Bone lesions: one or more osteolytic lesions 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., A

Exclusion Criteria

Patient with a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, plasma cell leukemia or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein <3 g/dL; clonal bone marrow plasma cells <10%, and absence of end-organ damage; or amyloidosis that can be attributed to the plasma cell proliferative disorder. Smoldering multiple myeloma is defined as serum monoclonal protein = 30 g/L or urinary monoclonal protein = 500 mg per 24 h and/or clonal bone marrow plasma cell 10-60% with absence of related organ or tissue impairment or endorgan damage or amyloidosis. Plasma cell leukemia is defined as the presence of circulating plasmacells (PCs) >2×10^9 /L in peripheral blood or a peripheral blood plasmacytosis >20%., Contraindication to any of the required concomitant drugs or supportive treatments., Pregnant or lactating females., Acute active infection requiring antibiotics or infiltrative pulmonary disease., Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the enrolment or place the subject at unacceptable risk, including acute diffuse infiltrative pericardial and pulmonary disease., Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs., Invasive malignancy within the past 5 years., Major surgery within 14 days before enrollment., Radiotherapy within 14 days before enrollment., Live vaccine 30 days before start of treatment and 90 days after the end of study treatment, Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment., Patient with a diagnosis of Waldenström’s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions., Participation in other clinical trials with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial., Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not., Patient has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment., Patient has peripheral neuropathy of grade 2 or higher as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 5.0., Patient is exhibiting clinical signs of meningeal involvement of multiple myeloma., Known to be: - seropositive for human immunodeficiency virus (HIV) - seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. - seropositive for hepatitis C (except in the setting of a sustained virologic response [SV