The study will enroll adult participants with RRMM who have been previously treated with at least 1 prior line of therapy, and who have documented disease progression during, or after, their most recent therapy. MedDRA version: 25.0 Level: LLT Classification code 10086466 Term: Relapsed/refractory multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
Czech Myeloma Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria are met: • Male or female, 18 years or older (at the time consent is obtained). • Confirmed diagnosis of multiple myeloma as defined by the IMWG criteria. • Previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy. Note: induction + ASCT + maintenance is 1 line of therapy. • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. • Participants with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met: o ASCT was >100 days prior to initiating study treatment, and o No active bacterial, viral, or fungal infection(s) present. • Must have at least ONE aspect of measurable disease, defined as one the following: o Urine M-protein excretion =200 mg/24h, or o Serum M-protein concentration =0.5 g/dL (=5.0 g/L), or o Serum free light chain (FLC) assay: involved FLC level =10 mg/dL (=100 mg/L) and an abnormal serum free light chain ratio (1.65). • All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0) must be = Grade 1 at the time of enrollment, except for alopecia. Adequate organ system function as defined by the below laboratory assessments. Hematologic o Absolute neutrophil count (ANC) =1.5 X 109/L; granulocyte colony-stimulating factor (G-CSF) use is NOT allowed to reach this level for the past 14 days. o Hemoglobin = 8.0 g/dL; without blood transfusions for the past 14 days, erythropoietin is allowed. o Platelet count =75 x 109/L; blood transfusions or platelet stimulating agents for the past 14 days are NOT allowed to reach this level. Hepatic o Total bilirubin =1.5xULN (isolated bilirubin =1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). o LT = 2.5xULN. Renal o eGFR =30 mL/min/1.73 m2; calculated using the Modified Diet in Renal Disease (MDRD) formula. o Spot urine (albumin/creatinine ratio) =500 mg/g (56 mg/mmol) OR o 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). • Female Participants: Contraceptive use by women 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 1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the intervention period and for 4 months after the last dose of belantamab mafodotin, and 7 months from the last dose of bortezomib, whichever is longer, 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. WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1. The investigator is responsible for review o
Exclusion criteria
Exclusion criteria: A participant will not be eligible for inclusion in this study if any of the following criteria are met: • Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed. • Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. • Prior treatment with anti-BCMA therapy. • Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic antimyeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter. • Plasmapheresis within 7 days prior to the first dose of study drug. • Has received radiotherapy to a large pelvic area (check with sponsor). Bridging radiotherapy otherwise is allowed. NOTE: Disease assessment should be repeated if RT is done prior to first dose of study drug within screening window. • Prior allogenic stem cell transplant. NOTE – Participants who have undergone syngeneic transplant will be allowed, only if no history of GvHD. • Any major surgery within 4 weeks prior to the first dose of study drug. Exception allowed for bone stabilizing surgery after consultation with medical monitor. • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures. • Evidence of active mucosal or internal bleeding. • Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria. • Previous or concurrent malignancies other than multiple myeloma, unless the second malignancy 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. NOTE: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction. • Evidence of cardiovascular risk including any of the following: Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including 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 before screening. • Class III or IV heart failure as defined by the New York Heart Association functional classification system • Uncontrolled hypertension. • Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, bortezomib, boron or mannitol or any other components of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To optimize the dosing and schedule of belantamab mafodotin in combination with Vd in RRMM in order to achieve similar efficacy and ensure improved toxicity profile;Secondary Objective: 1.To further assess the efficacy of belantamab mafodotin in combination with Vd 2.To further assess the safety of belantamab mafodotin in combination with Vd 3.To describe the exposure to belantamab mafodotin when administered in combination with bortezomib and dexamethasone 4.To evaluate an alternate corneal AE management approach in hands of hematologist;Primary end point(s): 1. ORR, defined as the percentage of participants with a Partial Response (PR) or better (i.e., PR, Very Good Partial Response (VGPR), Complete Response (CR), stringent Complete Response (sCR) ) 2. Incidence rate of Grade =3 ocular adverse events according to the keratopathy visual acuity (KVA) scale;Timepoint(s) of evaluation of this end point: NA | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Minimal Residual Disease (MRD) negativity rate, defined as the percentage of participants who are MRD negative by next-generation flow (NGF). 2. Time to Response (TTR), defined as the time between the date of first dose of study treatment and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better 3.Duration of Response (DoR), defined as the time from first documented evidence of PR or better until progressive disease (PD) or death due to PD among participants who achieve confirmed PR or better o 4. Progression-Free Survival (PFS), defined as the time from the date of first dose of study treatment until the earliest date of documented disease progression or death due to any cause 5.Overall survival (OS), is defined as the time between the date of the first dose of study treatment and death. 6.Concentration of belantamab mafodotin 7.Ocular findings on ophthalmic exam a)Cumulative event rate of ocular AEs to Week 16 (KVA scale) b)Incidence rate of ocular AEs by grade (KVA scale) c)Exposure adjusted incidence rate of ocular AEs by grade (KVA scale) d)Median duration of dose delay due to ocular AEs e)Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to ocular AEs f)Cumulative incidence of ocular AEs by grade g)Duration of ocular AEs h)Percentage of time on study with ocular AEs i)Change in best corrected visual acuity (BCVA) 8.Correlation of KVA grades with vision related anamnestic tool (Appendix 4);Timepoint(s) of evaluation of this end point: NA | — |
Countries
Czech Republic
Contacts
Public ContactClinical Trial Information
Czech Myeloma Group
Outcome results
None listed