Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Hepatic Impairment, Bortezomib, Dexamethasone, Belantamab mafodotin
Brief summary
The goal of the clinical trial is to collect safety data and information on how the body processes BVd in people with multiple myeloma (MM) who have moderate liver problems, compared with similar participants who have normal liver function. It also compares how liver problems affect the body's handling of belantamab mafodotin and uses the results to help set safe and appropriate dosing guidance for MM participants with moderate liver problems.
Interventions
DRUGBelantamab mafodotin
Belantamab mafodotin will be administered.
DRUGBortezomib
Bortezomib will be administered.
DRUGDexamethasone
Dexamethasone will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the informed consent form (ICF). * Has histologically or cytologically confirmed diagnosis of MM, as defined by the International Myeloma Working Group (IMWG). * Previously treated with at least 1 prior line of MM therapy and must have documented disease progression during or after their most recent therapy. * Has at least 1 aspect of measurable disease, defined as at least 1 of the following: 1. Urine M-protein excretion ≥200 milligram (mg)/24 hours (≥0.2 gram \[g\]/24 hours) 2. Serum M-protein concentration ≥0.5 g/ deciliter (dL) (≥5.0 g/L) 3. Serum Free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65). 4. Plasmacytoma measurable as per IMWG criteria 5. Bone Marrow infiltration by plasma cells \>30% * For those participants with a history of autologous stem cell transplant, they are eligible for study participation provided the following eligibility criteria are met: transplant was \>100 days prior to study enrollment; no active infection(s); participant meets the remainder of the eligibility criteria * All prior treatment-related toxicities (defined by National Cancer Institute Common terminology criteria for adverse events \[NCI-CTCAE\] v5.0) must be Grade ≤1 at the time of treatment assignment, except for alopecia (any grade), neuropathy (Grade ≤2), or endocrinopathy managed with replacement therapy (any grade). * Is willing to use adequate contraception male and female participants. * Female participants are eligible to participate if they are not pregnant or breastfeeding and meet additional requirements. * Is capable of giving signed informed consent including compliance with the requirements and restrictions listed in the ICF and protocol. * Has adequate organ function for hematological and renal function tests. * Has specific hepatic function ranges for serum bilirubin and AST for Group 1 and Group 2. * Participants in Group 1 (normal hepatic function) will only be enrolled if they match a participant in Group 2 (moderate hepatic impairment). Each Group 1/Group 2 pair will be matched based on the Group 2 participant's baseline body weight (±20%). * Participants with a history of Hepatitis B virus (HBV) and/or Hepatitis C virus (HCV) and Human immunodeficiency virus (HIV) exposure are eligible under specific conditions
Exclusion criteria
* Has an active plasma cell leukemia at the time of screening, symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), or Waldenström macroglobulinemia. * Has a previous or concurrent invasive malignancy other than MM, except for any other disease from which the participant must be considered medically stable for at least 1 year; or the participant must not be receiving active therapy, other than hormonal therapy for this disease. * 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. * Has evidence of active mucosal or internal bleeding. * Has a systemic active infection requiring treatment. * Has had any major surgery (other than bone-stabilizing surgery) within 28 days prior to the first dose of study treatment. * Has current corneal epithelial disease except for mild superficial keratopathy. * Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures. * Has any history of prior allogenic stem cell transplant. Participants who have undergone syngeneic transplant will be allowed only if no history of or no currently active graft versus host disease. * Has received prior belantamab mafodotin therapy if given within the last 90 days. * Has received treatment with an investigational agent within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study drug. This includes prior treatment with a monoclonal antibody and any other B-cell maturation antigen (BCMA) targeting therapy. The only exception is emergency use of a short course of systemic corticosteroids (equivalent to, or less than: dexamethasone 40 mg/day for a maximum of 4 days) before treatment. * Has received treatment with an inhibitor of Organic anion transporting polypeptide (OATP)1B1 or OATP1B3 within 14 days, preceding the first dose of study drug. * Has received plasmapheresis within 7 days prior to the first dose of study treatment. Screening laboratory values must be performed after last plasmapheresis. * Has received any live vaccine within 30 days of enrollment. Vaccination against COVID-19 using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary. * Has a known HIV infection, unless the participant meets all of the following criteria: 1. Established Anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load \<400 copies/milliliter (mL) prior to first dose. 2. Has CD4+ T-cell count values ≥350 cells/L 3. No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months. * Is pregnant, plans to become pregnant, or is breastfeeding. * Has Gilbert's syndrome. * Has current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice in the last 14 days prior to the first dose. * Has documented presence of Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb) at screening or within 3 months prior to the first dose of study intervention. Participants with hepatitis B will be excluded unless the specific protocol criteria are met. * Has a positive Hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to the first dose of study intervention unless HCV ribonucleic acid (RNA) is negative, indicating past resolved HCV infection, including participants who have undergone curative treatment, unless specific protocol criteria are met * Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention. * Evidence of cardiovascular risk including any of the following: 1. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities including second degree (Mobitz Type II) or third degree atrioventricular block. 2. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening. 3. Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. 4. Uncontrolled hypertension. * Has QT interval corrected (QTc) \>450 milliseconds (msec) or QTc \>480 msec for participants with bundle branch block
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC 0-tau) of belantamab mafodotin antibody drug conjugate (ADC) | Up to 3 weeks |
| Maximum observed plasma concentration (Cmax) of belantamab mafodotin ADC | Up to 3 weeks |
| Concentration at end of infusion (C-EOI) of belantamab mafodotin ADC | Up to 104 weeks |
| Drug concentration reached prior to next dose (Ctrough) of belantamab mafodotin ADC | Up to 104 weeks |
| Time to reach Cmax (Tmax) of belantamab mafodotin ADC | Up to 3 weeks |
| Area under the plasma concentration-time curve from time 0 to 168 hours (AUC 0-168h) of microtubule inhibitor released from belantamab mafodotin (cys-mcMMAF) | Up to 168 hours |
| Area under the plasma concentration-time curve from time 0 to 240 hours (AUC 0-240h) of cys-mcMMAF | Up to 240 hours |
| Cmax of cys-mcMMAF | Up to 3 weeks |
| Tmax of cys-mcMMAF | Up to 3 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) and serious AEs by severity | Up to 252 weeks | — |
| Number of participants with AEs leading to dose modifications or study intervention discontinuation | Up to 252 weeks | — |
| Number of participants with changes in visual acuity (VA) and corneal findings by severity as assessed by Keratopathy Visual Acuity scale (KVA) scale | Up to 252 weeks | The Keratopathy-Visual Acuity (KVA) scale is a 0-4 grading system used to assess the severity of keratopathy and its impact on visual acuity. Higher grades reflect increasing severity of corneal findings and visual acuity loss. |
| Number of participants with ocular AEs by severity as assessed by Common terminology criteria for adverse events (CTCAE) | Up to 252 weeks | — |
| Number of participants with thrombocytopenic events by severity | Up to 252 weeks | — |
| Change from baseline in clinical laboratory parameter: serum bilirubin (milligrams per decilitre[mg/dl]) | Baseline (Day 1) and up to 252 weeks | — |
| Change from baseline in clinical laboratory parameter: AST and ALT (International Units per litre [IU/L]) | Baseline (Day 1) and up to 252 weeks | Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) will be analysed. Both parameters have same unit of measure. |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed