YOUNG PATIENTS AFFECTED BY MULTIPLE MYELOMA (MM) TO THE DIAGNOSIS ELIGIBLE TO THE AUTOLOGOUS TRANSMISSION OF STEM CELLS MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: DARZALEX - 1800 MG- SOLUTION FOR INJECTION
Product Name: DARATUMUMAB
Product Code: JNJ-54767414
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DARATUMUMAB
CAS Number: 945
Sponsors
STITCHING EUROPEAN MYELOMA NETWORK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Patient at least 18 years of age and = 65 years. ? 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.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: - Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma - Measurable disease as defined by at least one of the following: ? serum M-protein level =1 g/dL or urine M-protein level =200 mg/24 hours; or ? 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: - 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 177 µmol/L (>2 mg/dL) - Anaemia: haemoglobin value of >20 g/L below the lower limit of normal, or haemoglobin value 1 focal lesion on MRI studies (each focal lesion must be 5 mm or more in size) ? Patient is, in the investigator(s) opinion willing and able to comply with the protocol requirements. ? 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 contrac
Exclusion criteria
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 2×109/L in peripheral blood or a peripheral blood plasmacytosis >20%. ? 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. ? 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) 4.0.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. ? Clinical active infectious hepatitis type A, B, C or HIV. ? Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] <60% of predicted normal), persistent asthma, or a history of asthma within the last 2 years. Subjects with known or suspected COPD or asthma must have a FEV1 test during screening. ? Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. ? Known allergy to any of the study medications, their analogues, or excipients in the various formulations. ? 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. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib. ? Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. ? Live vaccine 30 days before start of treatment and 90 days after the end of study treatment ? Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and thr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -Determine the progression free survival (PFS) at 36 months from first randomization (24 months from second). -Determine minimal residual disease (MRD) negativity rate after consolidation according to IMWG criteria, by means of next generation sequencing (NGS) -Determine MRD negativity rate during maintenance according to IMWG criteria, by means of next generation sequencing (NGS);Secondary Objective: Determine: overall response rate VGPR rate Determine the CR and sCR rate. PFS2 the safety the duration of response the overall survival the time to progression the time to next therapy MRD negativity rate by next generation flow cytometry (NGF) and PET/CT after induction, consolidation and during maintenance the role of MRD on OS the prognostic role of different sensitivity levels of MRD the MRD duration the conversion rate of MRD negativity in MRD positivity and viceversa whether tumor response and outcome may change in subgroups with different prognosis according to current prognostic factors whether tumor response and outcome may change in subgroups with different prognosis according to new prognostic factors the impact of maintenance treatment on MRD Determine whether tumor response and outcome may change in subgroups with different prognosis according to new prognostic factors, as evaluated by NGS. Definition of prognostic factors, as assessed by NGS Evaluate QoL ;Primary end point(s): -Progression free survival (PFS) -MRD negativity;Timepoint(s) of evaluation of this end point: NA | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall response rate (ORR) -Progression free survival 2 (PFS2) - Duration of response (DoR) - Overall survival (OS) - Time to progression (TTP) - Time to the next anti-myeloma therapy (TNT) -MRD by NGF and PET/CT -Definition of prognostic factors, as assessed by NGS (MM-panel);Timepoint(s) of evaluation of this end point: NA | — |
Countries
Czechia, Czech Republic, Greece, Italy
Contacts
Public ContactMario Boccadoro
EMN Trial Office S.r.l. Impresa Sociale
Outcome results
None listed