ISATUXIMAB for Multiple myeloma (newly diagnosed)

Inclusion criteria

• {"criterion_text":"- Patient is, in the investigator’s opinion, willing and able to comply with the protocol requirements."}
• {"criterion_text":"- Male patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies."}
• {"criterion_text":"- All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤ Grade 1 at the time of enrolment except for alopecia."}
• {"criterion_text":"- Patient must be able to understand the study procedures."}
• {"criterion_text":"- Patient has given voluntary written informed consent before performance of any study-related procedure non part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care."}
• {"criterion_text":"- Newly diagnosed multiple myeloma patient who requires start active treatment according to the 2014 IMWG criteria, namely clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: Hypercalcaemia, Anaemia, Renal Insufficiency, or Bone lesions (one or more osteolytic lesions on skeletal radiography, CT, or PET-CT), and any one or more of the following biomarkers: clonal BMPC% ≥60%, i/u free light ratio ≥100 or > 1 focal lesions on MRI or PET/CT) [Lancet Oncol. 2014;15(12): e538-e548]"}
• {"criterion_text":"- Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio."}
• {"criterion_text":"- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2."}
• {"criterion_text":"- Patient must be ≤ 65 years of age."}
• {"criterion_text":"- Patient must have adequate organ function, defined as table 2 in protocol."}
• {"criterion_text":"- Female patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies"}

Exclusion criteria

• {"criterion_text":"- Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening."}
• {"criterion_text":"- Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy."}
• {"criterion_text":"- Patient has peripheral neuropathy or neuropathic pain grade 1 with pain or ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0"}
• {"criterion_text":"- Patient evidence of cardiovascular risk including any of the following: • Myocardial infarction within 6 months before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV). • Uncontrolled cardiac arrhythmia. • Screening 12-lead ECG showing a baseline interval QTcF> 470 msec (exception: subjects with pacemaker). • Patients with uncontrolled hypertension."}
• {"criterion_text":"- Patients who have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis."}
• {"criterion_text":"- Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria."}
• {"criterion_text":"- Evidence of active mucosal or internal bleeding."}
• {"criterion_text":"- Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form."}
• {"criterion_text":"- Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months)."}
• {"criterion_text":"- Patient with acute diffuse infiltrative pulmonary disease and/or pericardial disease."}
• {"criterion_text":"- Patient with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%."}
• {"criterion_text":"- Patient has had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma."}
• {"criterion_text":"- History of interstitial lung disease or ongoing interstitial lung disease."}
• {"criterion_text":"- Subject has gastrointestinal disease that may significantly alter the absorption of iberdomide and/or other oral study treatment."}
• {"criterion_text":"- Patient has an active infection requiring systemic antibiotic, antiviral, or antifungal treatment at the time of starting treatment."}
• {"criterion_text":"- Patient has known HIV infection."}
• {"criterion_text":"- Patient seropositive for hepatitis B defined by a positive test for hepatitis B surface antigen (HBsAg). Subjects with resolved infection (i.e., 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 PCR measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Subjects who were positive only for HBsAg and had a valid vaccination certificate for hepatitis B could be included in the stutjdy, without the need to determine an undetectable HBV viral load."}
• {"criterion_text":"- Patient has positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained."}
• {"criterion_text":"- Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required Patient require concurrent administration of a strong inhibitor or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment)"}
• {"criterion_text":"- Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to iberdomide or drugs chemically related to iberdomide."}
• {"criterion_text":"- Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to isatuximab or drugs chemically related to isatuximab, hypersensitivity reactions, or idiosyncratic reactions to other molecular antibodies."}
• {"criterion_text":"- Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to lenalidomide or dexamethasone or drugs chemically related to lenalidomide or dexamethasone."}
• {"criterion_text":"- Prior history of malignancies, other than multiple myeloma (except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or the breast), unless the patient has been free of the disease for ≥ 5 years."}
• {"criterion_text":"- Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and/or lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment."}
• {"criterion_text":"- Pregnant or breastfeeding females."}
• {"criterion_text":"- Men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception)."}
• {"criterion_text":"- Patient is simultaneously enrolled in other interventional clinical trial."}
• {"criterion_text":"- Patient has used an investigational drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug."}
• {"criterion_text":"- Patient must not have received prior radiotherapy (except localized palliative radiotherapy for pain, palliation or fracture) within 2 weeks of start of study therapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis."}

Primary endpoints

• {"endpoint_text":"- Improvement in the percentage of patients MRD-negative in Arm A vs. Arm B when considering B1 endpoint. B1 endpoint: VRD extended impact only, without considering ERI impact: any patient that require an ERI per protocol before finishing the 18 cycles + ASCT, will be considered MRD-positive at that time, independently of the ERI impact","definition_or_measurement_approach":"MRD negativity assessed by next-generation flow cytometry (NGF) after 18 cycles + ASCT; B1 considers VRD extended impact only and classifies patients who receive ERI prior to finishing 18 cycles + ASCT as MRD-positive at that time."}
• {"endpoint_text":"- Non-inferiority in the percentage of patients MRD-negative in Arm A vs. Arm B when considering B2 endpoint. B2 endpoint: VRD extended plus ERI impact: any patient who achieves MRD negativity with ERI before finishing the 18 cycles + ASCT will be considered MRD-negative at that time.","definition_or_measurement_approach":"MRD negativity assessed by NGF after 18 cycles + ASCT; B2 considers VRD extended plus ERI impact and counts patients who achieve MRD-negativity with ERI before finishing 18 cycles + ASCT as MRD-negative."}

Other endpoints

• {"endpoint_text":"- Other secondary objectives 2.4 Progression-Free Survival (PFS) 2.5 Overall Response Rate (ORR): PR or better (PR, VGPR, CR, sCR). 2.6 Complete Response Rate (CRR): CR or better (CR, sCR). 2.7 Time to Response (TTR), among participants who achieve confirmed PR or better. 2.8 Duration of Response (DoR) among participants who achieved PR or better. 2.9 PFS2 2.10 Overall Survival (OS)","definition_or_measurement_approach":"PFS, ORR (PR or better including VGPR, CR, sCR), CRR (CR or better), TTR among those with confirmed PR or better, DoR among responders, PFS2, and OS as defined in protocol (standard oncology efficacy endpoints)."}

Spain

Earliest CTIS Part Ii Submission Date

15-10-2024

Latest Decision Or Authorization Date

29-08-2025

Processing Time Days

318

Number Of Participants

480

Primary sponsor

Full Name

Fundacion PETHEMA

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Distefar Del Sur S.L.","duties_or_roles":"Medication Logistics","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Start From Scratch S.L.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Adknoma Health Research S.L.","duties_or_roles":"ASR reporting","organisation_type":"Pharmaceutical company"}