Health Condition 1: C900- Multiple myeloma
Conditions
Interventions
Intervention1: Study Drugs : Belantamab mafodotin, Lenalidomide and Dexamethasone
: Experimental (Arm A) : Belantamab mafodotin 1.9 mg/kg IV will be administered Q8W for first 24 weeks, then 1.9 mg/
Sponsors
GlaxoSmithKline Research & Development Limited
Pharmaceutical Research Associates India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Is at least 18 years or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent. 2.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the protocol. 3. Newly Diagnosed MM with a requirement for treatment as documented per IMWG criteria. 4. Must have at least 1 aspect of measurable disease, as assessed by the central laboratory, defined as 1 of the following: i) Urine M-protein excretion more than or equal to 200 mg/24 hours (more than or equal to 0.2 g/24 hours) And/or ii) Serum M-protein concentration more than or equal to 0.5 g/dL (more than or equal to 5.0 g/L) And/or iii) Serum free light-chain (FLC) assay: involved FLC level more than or equal to 10 mg/dL (more than or equal to 100 mg/L) and an abnormal serum FLC ratio (less than 0.26 or more than 1.65). 5. Newly diagnosed and not considered candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT) due to any of the following: i)Exclusion from treatment with ASCT due to country or site-specific age restriction. ii)Presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT. 6.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 7.Adequate organ system function as defined by the laboratory assessments. 8.Male participants: i) Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. ii) Male participants are eligible to participate if they agree to the following during the Treatment Period and for at least 6 months after the last dose of study intervention to allow for clearance of any altered sperm: Refrain from donating fresh unwashed semen 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. iii) 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 less than 1% per year when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Male participants should also use a condom when having sexual intercourse with pregnant females. 9. Female participants: i) Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. ii) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1% per year), preferably with low user dependency during the Treatment Period and for 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. iii) A WOCB
Exclusion criteria
Exclusion criteria: 1. Diagnosis of systemic amyloid light chain amyloidosis, Waldenstrom disease, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or Primary Plasma Cell Leukemia (defined as circulating plasma cells more than 5%). 2.Prior systemic therapy for multiple myeloma, or smoldering multiple myeloma. 3.Signs of meningeal or central nervous system involvement with multiple myeloma. 4.Major surgery within 2 weeks prior to the first dose of study drugs or has not recovered fully from surgery. Kyphoplasty is not considered major surgery. 5.Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant safety, obtaining informed consent, or compliance with study procedures. 6.Current active liver or biliary disease (except for Gilbert syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the investigator assessment). 7.Participants with previous or concurrent malignancies other than multiple myeloma are excluded. Exceptions are any other malignancy that has been considered medically stable for at least 2 years, after discussion with the GSK Medical Monitor. The participant must not be receiving active therapy, other than hormonal therapy for this disease. 8.Evidence of cardiovascular risk including any of the following: i)Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second-degree (Mobitz Type II) or third-degree atrioventricular block. ii)Recent history (within 3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty or stenting, or bypass grafting. iii)Class III or IV heart failure as defined by the New York Heart Association functional classification system. 9.Known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria: i)Established antiretroviral therapy for at least 4 weeks and HIV viral load less than 400 copies/mL within Screening Period. ii)CD4+ T-cell (CD4+) counts more than or equal to 350 cells / micro Litre. iii) No history of acquired immune deficiency syndrome-defining opportunistic infections within the last 12 months. 10.Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention unless the participant can meet the following criteria: i)RNA test negative. ii)Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C viral load RNA test after a washout period of at least 4 weeks. 11. Participants with hepatitis B will be excluded unless the defined criteria can be met. 12. Current corneal epithelial disease except for mild punctate keratopathy. 13. Intolerance or contraindications to antiviral prophylaxis. 14. Unable to tolerate antithrombotic prophylaxis. 15. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study intervention. 16. Plasmapheresis within 7 days prior to the first dose of study intervention. <br/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. PFS: Defined as the time from the date of randomization to the date of first documented PD per International Myeloma Working Group (IMWG) criteria by Independent Review Committee (IRC) or death from any cause in the absence of progression, whichever occurs first. 2. Number of Participants Achieving MRD Negative Status: Defined as achieving MRD negativity at 10^-5 sensitivity threshold (1 nucleated tumor cell in 100,000 normal cells) assessed by next-generation sequencing (NGS) at least once during the time of confirmed complete response (CR) or better response per IMWG criteria by IRC.Timepoint: Up to approximately 7 years | — |
Secondary
| Measure | Time frame |
|---|---|
| PFS2 : Defined as the time from the date of randomization to the date of documented PD following the first subsequent anti-myeloma therapy or death from any cause, whichever is earlier.Timepoint: Up to approximately 7 years;Overall Survival (OS)Timepoint: Up to approximately 7 years;Number of Participants Achieving CR or Better (CR+)Timepoint: Up to approximately 7 years;Number of Participants Achieving Very Good Partial Response (VGPR) or BetterTimepoint: Up to approximately 7 years;Number of Participants Achieving Sustained MRD Negative StatusTimepoint: Up to approximately 7 years;Duration of Response (DoR)Timepoint: Up to approximately 7 years;Time to Second Next Line Therapy (TTST)Timepoint: Up to approximately 7 years;Number of Participants With Adverse Events (AEs)Timepoint: Up to approximately 7 years;Number of Participants With Ocular Findings on Ophthalmic ExamTimepoint: Up to approximately 7 years;Maximum Post-baseline Patient-Reported Outcomes Version of the Common Term Criteria for Adverse Events (PRO-CTCAE) ScoreTimepoint: Up to approximately 7 years;Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30Timepoint: Up to approximately 7 years;Change From Baseline in EORTC QLQ-MY20Timepoint: Up to approximately 7 years;Plasma Concentrations of Belantamab MafodotinTimepoint: Up to approximately 7 years;Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Belantamab MafodotinTimepoint: Up to approximately 7 years;Titers of ADAs Against Belantamab MafodotinTimepoint: Up to approximately 7 years | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Norway, Poland, Republic of Korea, South Africa, Spain, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactSuhail Ahmad
Pharmaceutical Research Associates India Private Limited
Outcome results
None listed