Relapsed/Refractory Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form 2. Male or female, 18 years or older (at the time consent is obtained) 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix 8 of the protocol) 4. Histologically or cytologically confirmed diagnosis of MM as defined according to IMWG, [Rajkumar, 2014] criteria, and a) Has undergone stem cell transplant or is considered transplant ineligible, and b) Has failed at least 3 prior lines of anti-myeloma treatments, including an anti- CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to an IMiD (i.e., lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). The number of prior lines of therapy will be determined according to the guidelines in Rajkumar 2015. 5. Has measurable disease with at least one of the following: a. Serum M-protein =0.5 g/dL (=5 g/L) b. Urine M-protein =200 mg/24h c. Serum FLC assay: Involved FLC level =10 mg/dL (=100 mg/L) and an abnormal serum free light chain ratio (1.65) 6. Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a. transplant was >100 days prior to study enrolment b. no active infection(s) c. participant meets the remainder of the eligibility criteria outlined in this protocol 7. Adequate organ system functions as defined in Table 9 of the protocol p55. 8. Female Participants: Contraceptive use by men or 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 one 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 at least 80 days 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. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 9. Male Participants: Contraceptive use by men or women 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 for at least 140 days: - 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 a
Exclusion criteria
Exclusion criteria: Participants satisfying any of these criteria are not eligible for assignment to treatment: 1. Systemic anti-myeloma therapy within 480 msecs (the QT interval values must be corrected for heart rate by Fridericia’s formula [QTcF]) b. Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block. c. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening. d. Class III or IV heart failure as defined by the New York Heart Association functional classification system [NYHA, 1994] e. Uncontrolled hypertension 14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment. 15. Pregnant or lactating female. 16. Active infection requiring antibiotic, antiviral, or antifungal treatment. 17. Known HIV infe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical efficacy of 2 doses of belantamab mafodotin in participants with relapsed/refractory multiple myeloma;Secondary Objective: - To further evaluate the clinical measures of efficacy of belantamab mafodotin in participants with RRMM - To evaluate the safety of belantamab mafodotin in participants with RRMM. - To evaluate the pharmacokinetic profile of belantamab mafodotin - To assess anti-drug antibodies (ADAs) against belantamab mafodotin - Participant self-reported symptomatic adverse effects by evaluation of tolerability of belantamab mafodotin - To evaluate disease and treatment related symptoms and impact on function and health-related quality-of-life;Primary end point(s): ORR, defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, very good partial response [VGPR], complete response [CR] and stringent complete response [sCR]), according to the 2016 International Myeloma Working Group (IMWG) Response Criteria by Independent Review Committee (IRC).;Timepoint(s) of evaluation of this end point: Every 3 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ORR, defined as the percentage of participants with a confirmed partial response (PR) or better, according to the 2016 International Myeloma Working Group (IMWG) Response Criteria by investigator assessment. Clinical benefit rate (CBR), defined as the percentage of participants with a confirmed minimal response (MR) or better according to the 2016 International Myeloma Working Group (IMWG) Response Criteria. Duration of response (DoR), defined as: the time from first documented evidence of PR or better until the earliest date of documented disease progression (PD) per IMWG; or death due to PD occurs among participants who achieve an overall response, i.e., confirmed PR or better. Time to response, defined as the time between the date of randomization and the first documented evidence of response (PR or better). Progression-free survival, defined as the time from randomization until the earliest date of documented disease progression (PD) per IMWG, or death due to any cause. Time to progression, defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD. Overall survival, defined as the time from first dose until death due to any cause. The safety profile of belantamab mafodotin will be evaluated in participants with RRMM as assessed through: standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests) through the collection of adverse events (AEs) and serious adverse events (SAEs) AEs of special interest ocular findings on ophthalmic exam Plasma concentrations of belantamab mafodotin (ADC, total mAb and cys-mcMMAF) Derived pharmacokinetic parameter values (e.g., AUC, Cmax, tmax, t½), as data permit. Incidence and titers of ADAs against belantamab mafodotin Symptomatic adverse effects and related impacts as measured by the PRO-CTCAE, NEI-VFQ-25 and OSDI Health-related quality-of-life as measured by the EORTC QLQ | — |
Countries
Australia, Canada, France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed