Isatuximab for Multiple myeloma|High-risk multiple myeloma

Inclusion criteria

• {"criterion_text":"- 1. Subjects must have newly diagnosed, untreated, symptomatic (according to the revised CRAB criteria 2014), documented myeloma and have measurable disease (serum M-protein ≥ 1 g/dL (for IgA ≥ 0.5 g/dL) or urine M-protein ≥ 200 mg/24 hours) or in case of oligosecretory myeloma: involved FLC level ≥ 10 mg/dL, provided sFLC ratio is abnormal or in case of asecretory myeloma: > 1 focal lesions measurable by MRI Subjects must have high-risk myeloma defined as followed: •\tPresence of one or more of the following cytogenetic abnormalities (determined by FISH): -\tDel(17p) in ≥ 10% of purified cells -\tt(4;14) -\t≥ 3 copies +1q21 -\tt(14;16) •\tISS Stage II or III (all patients)\n- 2.\tMust be ≥ 18 years at the time of signing the informed consent form.\n- 3.\tMust be able to adhere to the study visit schedule and other protocol requirements in the investigator’s opinion.\n- 4.\tWHO performance status 0-3 (WHO=3 is allowed only if caused by MM and not by co-morbid conditions)\n- 5.\tFemales of childbearing potential (FCBP) (1) must agree to refrain from becoming pregnant for 28 days prior to initiation of study drug, while on study drug and for 150 days* after discontinuation from the study drug by using 2 reliable methods of contraception and must agree to regular pregnancy testing during this timeframe. (1) A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months) 3) has achieved menarche at some point.\n- 6.\tFemales must agree to abstain from breastfeeding during study participation and 30 days* after study drug discontinuation.\n- 7.\tMales must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 150 days* following discontinuation from this study, even if he has undergone a successful vasectomy.\n- 8.\tMales must also agree to refrain from donating semen or sperm while on treatment with any study drug and for 150 days* after discontinuation from this study treatment.\n- 9.\tAll subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.\n- 10.\tAll subjects must agree not to share medication.\n- 11.\tAll participating subjects have to follow the requirements of the Lenalidomide Pregnancy Prevention Plan"}

Exclusion criteria

• {"criterion_text":"- 1.\tContraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize Carfilzomib), mannitol, sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.\n- 2.\tPatients with known systemic amyloidosis (except for AL amyloidosis of the skin or the bone marrow)\n- 3.\tAdministration of systemic chemotherapy, biological, immunotherapy or any investigational agent (therapeutic or diagnostic) for multiple myeloma except bisphosphonate therapy. Emergency treatment with dexamethasone is allowed when the cumulative dexamethasone dose is less or equal 160 mg. It is allowed to include patients in the trial after 1 cycle (4 weeks) of any anti-myeloma first-line treatment.\n- 4.\tAny of the following laboratory abnormalities: o\tAbsolute neutrophil count (ANC) < 1,000/μL, unless related to myeloma o\tPlatelet count < 30,000/ μL (in case of platelets < 50.000 /µL and ≥ 30.000 /µL myeloma bone marrow infiltration should be ≥ 50%) o\tCorrected serum calcium > 14 mg/dL (> 3.5 mmol/L); or free ionized calcium > 6.5 mg/dL (> 1.6 mmol/L) o\tSerum GOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN) or serum total bilirubin > 2.0 mg/dL if not due to hereditary abnormalities as Gilbert’s disease or hereditary hemolysis (Note: if the mentioned limits for bilirubin or ASAT/ALAT are exceeded, but there is no significant hepatic dysfunction at investigator’s discretion, the study office has to be consulted prior to inclusion) o\tPatients with severe renal impairment (eGFR < 30 mL/min/1.73 m², MDRD formula or CDK-EPI or Creatinine Clearance < 30 mL/min)\n- 5.\tActive congestive heart failure (NYHA Class III to IV), symptomatic cardiac ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior study entry.\n- 6.\tKnown HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B sAg and core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed). Patients with a history of hepatitis B infection have to be monitored repetitively during treatment. In case of signs of hepatitis B reactivation, antiviral treatment has to be initiated and patients have to be referred to a specialist for treatment and monitoring of hepatitis infection.\n- 7.\tAcute active, uncontrolled infection\n- 8.\tSignificant neuropathy (Grades 3 to 4, or Grade 2 with pain according CTC V4.03)\n- 9.\tSecond malignancy within the past 5 years except: - adequately treated basal cell or squamous cell skin cancer - carcinoma in situ of the cervix - prostate cancer Gleason Score ≤ 6 with stable PSA over the past 12 months - breast carcinoma in situ with full surgical resection - treated medullary or papillary thyroid cancer\n- 10.\tPatients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to study entry.\n- 11.\tMajor surgery within 4 weeks prior to cycle 1 day 1 (kyphoplasty is not considered major surgery); subjects should have been fully recovered from any surgical related toxicities.\n- 12.\tFemale patients who are pregnant or lactating\n- 13.\tAny other clinically significant medical disease or psychiatric condition that, in the Investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent.\n- 14.\tParticipation in any other clinical trial (with the exclusion of observational, non-interventional studies)."}

Primary endpoints

• {"endpoint_text":"- MRD negativity (sensitivity 10^-5, NGF) after consolidaton","definition_or_measurement_approach":"Measured by MRD assessment using next-generation flow / 8-color flow cytometry with sensitivity 10^-5 after consolidation"}

Secondary endpoints

• {"endpoint_text":"- Progression free survival","definition_or_measurement_approach":""}

Other endpoints

• {"endpoint_text":"- To evaluate Overall Response Rate (ORR)\n- To assess duration of minimal residual disease state\n- To evaluate overall survival\n- To assess time to subsequent therapy\n- To evaluate progression-free survival on next line therapy (PFS2)\n- To assess time to myeloma response\n- Quality of life assessment of patients at baseline, during induction treatment, consolidation and maintenance treatment","definition_or_measurement_approach":"Endpoints listed in secondary objectives; specific measurement methods not detailed in available data (e.g., ORR assessed by standard response criteria; QoL assessed at baseline and during treatment but instruments not specified)."}

Germany

Earliest CTIS Part Ii Submission Date

21-06-2024

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

472

Number Of Sites

17

Number Of Participants

246

Primary sponsor

Full Name

University Medical Center Hamburg-Eppendorf

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Amgen Limited","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Sanofi-Aventis Recherche & Development","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"Celgene International II Sárl","duties_or_roles":"","organisation_type":""}