BELANTAMAB MAFODOTIN for Newly diagnosed multiple myeloma

Inclusion criteria

• {"criterion_text":"- 1.Participant aged 18 years or older\n- 2.Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma and documented MM satisfying at least 1 of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria: CRAB criteria: v.Hypercalcemia: serum calcium>0.25 mmol/L (>1 mg/dL) higher than ULN or >2.75 mmol/L(>11 mg/dL) vi.Renal insufficiency: creatinine clearance<40mL/min or serum creatinine>177 μmol/L(>2 mg/dL) vii.Anemia: hemoglobin>2 g/dL below the lower limit of normal or hemoglobin <10 g/dL viii.Bone lesions: 1 or more osteolytic lesions on skeletal radiography, CT, or PET-CT Any 1 or more of the following biomarkers of malignancy: a.Clonal bone marrow plasma cell percentage ≥60% b.Involved: uninvolved serum FLC ratio ≥100 c. More than 1 focal lesion on MRI studies\n- 3.Must have at least ONE aspect of measurable disease, defined as 1 of the following: Urine M-protein excretion≥200 mg/24 hrs (≥0.2g/24 hrs), or Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or Serum FLC assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)\n- 4.Not a candidate for high-dose chemotherapy with ASCT due to presence of significant comorbid condition(s), such as cardiac, pulmonary or other major organ dysfunction that are likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. The patients will be assessed with the IMWG frailty index, a scoring system based on age, comorbidities and cognitive and physical conditions, which is recommended by the ESMO guidelines [11]. Patients with IMWG frailty index score 1 or 2 will be considered transplant ineligible. The reason(s) for transplant ineligibility will be collected in the CRFs\n- 5.ECOG status of 0-2\n- 6.Adequate organ system function as defined by the below laboratory assessments Hematologic: Absolute neutrophil count (ANC) ≥1.5 X 10^9/L; GCSF use is NOT allowed to reach this level Hemoglobin ≥ 8.0 g/dL; transfusions are permitted Platelet count ≥ 50 x 10^9/L if bone marrow is >50% involved in myeloma Otherwise ≥75 x 10^9/L; transfusions are NOT allowed to reach this level Hepatic: Total bilirubin ≤1.5X ULN (Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) ALT ≤ 2.5 X ULN Renal: eGFR ≥30 mL/min/1.73 m^2; calculated using the Modified Diet in Renal Disease (MDRD) formula Spot urine (albumin/creatinine ratio) <500 mg/g (56 mg/mmol) OR Urine Dipstick: Negative trace; if ≥1+ only eligible if confirmed <500 mg/g [56 mg/mmol] by albumin/creatinine ratio (spot urine from first void)\n- 7.Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: •Is not a woman of childbearing potential (WOCBP) OR •Is a WOCBP and using two methods of reliable birth control (one method that is highly effective and one additional effective [barrier] method), beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use one method of reliable birth control that is highly effective for a further 4 months following discontinuation of belantamab mafodotin. WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during dose interruptions and for 28-days following the last dose of lenalidomide or 4 months following discontinuation of belantamab mafodotin treatment whichever is longer\n- 8.Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies: Male participants are eligible to participate if they agree to the following during the intervention period and until 28 days after the last dose of lenalidomide or 6 months after the last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm •Refrain from donating sperm PLUS either: •Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR •Must agree to use contraception/barrier as detailed below: Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females)\n- 9.Participants must be able to understand the study procedures and agree to participate in the study by providing written informed consent"}

Exclusion criteria

• {"criterion_text":"- 1.Prior systemic therapy for MM, or smoldering MM (SMM).\n- 10.Class III or IV heart failure as defined by the New York Heart Association functional classification system.\n- 11.Uncontrolled hypertension.\n- 12.Active infection requiring treatment.\n- 13.Known human immunodeficiency virus HIV infection, unless the participant can meet all of the following criteria: •Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL. •CD4+ T-cell (CD4+) counts ≥350 cells/uL. •No history of AIDS-defining opportunistic infections within the last 12 months.\n- 14. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]).\n- 15.Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of the study treatment unless the participant can meet the following criteria: •RNA test negative •Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis c virus (HCV) RNA test after a washout period of at least 4 weeks.\n- 16.Current corneal epithelial disease except for mild punctate keratopathy.\n- 17.Intolerance or contraindications to anti-viral prophylaxis.\n- 18.Unable to tolerate antithrombotic prophylaxis.\n- 19.AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.\n- 2.Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute , Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.\n- 20.Exhibiting clinical signs of or with a known history of meningeal or central nervous system involvement by multiple myeloma.\n- 21.Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.\n- 22.Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.\n- 23.Plasmapheresis within 7 days before the first dose of study drug.\n- 3.Major surgery within 4 weeks before the first dose of study drug.\n- 4.Presence of active renal condition (infection, requirement for dialysis or any other significant condition that could affect the participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided that they fulfil the other inclusion criteria.\n- 5.Any serious and/or unstable pre-existing medical or, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance with the study procedures.\n- 6.Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.\n- 7.Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the Investigator's assessment).\n- 8.Participants with previous or concurrent malignancies other than multiple myeloma. Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy that has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease.\n- 9.Evidence of cardiovascular risk including any of the following: •Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities, second degree (Mobitz Type II) or third degree atrioventricular (AV) block. •History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening."}

Primary endpoints

• {"endpoint_text":"- Part 1 Number of participants with dose-limiting toxicities (DLTs). Number of participants with adverse events (AEs) and serious adverse events (SAEs). Part 2 Overall Response rate as per International Myeloma Working Group (IMWG) by Investigator Assessment. Number of participants with adverse events (AEs) and serious adverse events (SAEs).","definition_or_measurement_approach":"Part 1: count of participants with DLTs; counts of AEs and SAEs. Part 2: Overall Response Rate (ORR) assessed per IMWG criteria by Investigator Assessment; counts of AEs and SAEs."}

Secondary endpoints

• {"endpoint_text":"- Lenalidomide relative Dose Intensity (RDI).","definition_or_measurement_approach":"Relative dose intensity of lenalidomide as reported (no further definition in provided text)."}
• {"endpoint_text":"- Cumulative administered dose of belantamab mafodotin in combination with lenalidomide and dexamethasone (Rd)","definition_or_measurement_approach":"Cumulative administered dose aggregated for belantamab mafodotin when given in combination with lenalidomide and dexamethasone."}
• {"endpoint_text":"- Time to Response (TTR) as per IMWG by Investigator Assessment.","definition_or_measurement_approach":"Time from treatment start to first documented response per IMWG as assessed by the investigator."}
• {"endpoint_text":"- Duration of Response (DoR) as per IMWG by Investigator Assessment.","definition_or_measurement_approach":"Time from first documented response to progression or death per IMWG as assessed by the investigator."}
• {"endpoint_text":"- Complete Response Rate (CRR) as per IMWG by Investigator Assessment.","definition_or_measurement_approach":"Complete response rate assessed per IMWG criteria by investigator assessment."}
• {"endpoint_text":"- MRD negativity rate in the bone marrow (BM), defined as the number (%) of participants who achieve MRD negativity (at or below the threshold of 10-5), assessed via NGF. MRD will be assessed via nextgeneration flow (NGF) cytometry.","definition_or_measurement_approach":"MRD negativity defined as at or below threshold of 10^-5 assessed via next-generation flow cytometry (NGF)."}
• {"endpoint_text":"- Progression Free Survival (PFS) as per IMWG by Investigator Assessment","definition_or_measurement_approach":"PFS assessed per IMWG criteria by investigator (time from randomization/treatment to progression or death)."}
• {"endpoint_text":"- Overall Survival (OS).","definition_or_measurement_approach":"Overall survival (time from randomization/treatment to death from any cause)."}
• {"endpoint_text":"- Number of participants with abnormal ocular findings (on ophthalmic exam).","definition_or_measurement_approach":"Count of participants with abnormal findings on ophthalmic examinations."}
• {"endpoint_text":"- Derived PK parameter values for belantamab mafodotin ADC.","definition_or_measurement_approach":"Pharmacokinetic parameters derived from blood sampling for belantamab mafodotin ADC (no further detail provided)."}
• {"endpoint_text":"- Number of participants with changes from baseline and proportion of participants with within-participant meaningful change in self reported ocular symptoms and related impacts as measured by the OSDI questionnaire (Part 1only).","definition_or_measurement_approach":"Changes in patient-reported ocular symptoms measured by the Ocular Surface Disease Index (OSDI) questionnaire (Part 1 only)."}
• {"endpoint_text":"- Number of participants with changes from baseline and proportion of participants with within-participant meaningful change in ocular symptoms and related impacts as measured by the Vision Related Anamnestic Tool (Part 2 only)","definition_or_measurement_approach":"Changes in ocular symptoms measured by the Vision Related Anamnestic Tool (Part 2 only)."}

Greece

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

21-10-2025

Processing Time Days

389

Number Of Sites

1

Number Of Participants

66

Primary sponsor

Full Name

Hellenic Society Of Hematology

Organisation Type

Patient organisation/association

Country Of Registered Address

Greece

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

Pharmacokinetics analysis (ADC, total mAb) in blood samples

Name

Almac Clinical Services Limited

Name

Health Data Specialists Ireland Limited

Responsibilities

Contracts with sites and vendors

Third parties

• {"country":"Ireland","full_name":"Health Data Specialists Ireland Limited","duties_or_roles":"Codes: 1,10,11,12,15 (Contracts with sites and vendors),6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"Pharmacokinetics analysis, biomarkers analysis, sBCMA; code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.","duties_or_roles":"Codes: 1,12","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Genotypos Private Diagnostic Laboratory Of Molecular And Cytogenetic Analysis S.A.","duties_or_roles":"(Fluorescence in situ hybridization) FISH, HBV DNA; code: 15","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Greece","full_name":"Panagiotis Desiris","duties_or_roles":"Ophthalmological analysis","organisation_type":"Health care"}
• {"country":"Greece","full_name":"National And Kapodistrian University Of Athens","duties_or_roles":"MRD for the analysis of the minimal residual disease clone","organisation_type":"Educational Institution"}
• {"country":"Greece","full_name":"Omma Ofthalmologiko Institouto Athinon Idiotiki M.I.N. S.A.","duties_or_roles":"Codes: 13; Ophthalmological exams","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Greece","full_name":"Nicotian Haemodiagnosi Med E.E.","duties_or_roles":"High-sensitivity Troponin T, NT-proBNP, Serum Free Light Chain; Primary/ surrogate endpoint test; Clinical haematology","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Glaxo Operations UK Limited","duties_or_roles":"Code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"Serum protein electrophoresis (sPEP) Urine protein electrophoresis (uPEP) Serum protein immunofixati","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Pharmacokinetics analysis (ADC, total mAb) in blood samples","organisation_type":"Pharmaceutical company"}