Multiple Myeloma
Conditions
Keywords
Relapsed-Refractory Multiple Myeloma, DREAMM-15, Belantamab Mafodotin, Blenrep, Pomalidomide, Bortezomib, Carfilzomib, Dexamethasone
Brief summary
This study is for adults with multiple myeloma (a type of blood cancer) that has come back after being treated earlier or isn't responding to the current treatment. The main goal is to find out if the study drug, belantamab mafodotin, given less often (on an extended schedule) with other cancer medicines, can still treat the cancer effectively while causing fewer side effects, especially those affecting the eyes. The study will also look at how well the treatment works overall and how safe it is when administered to the participants.
Interventions
DRUGBelantamab mafodotin
Belantamab mafodotin will be administered.
DRUGDexamethasone
Dexamethasone will be administered.
DRUGPomalidomide
Pomalidomide will be administered.
DRUGBortezomib
Bortezomib will be administered.
DRUGCarfilzomib
Carfilzomib 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
• Participants are eligible to be included in the study only if all of the following criteria apply: Applicable to All Arms - BPd, BVd, BKd: * Male or female, 18 years or older (at the time consent is obtained). * Have a confirmed diagnosis of Multiple Myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of zero to 2. * Have been previously treated with at least 1, but no more than 2, prior lines of MM therapy and must have documented disease progression during or after their most recent therapy. * Must have at least 1 aspect of measurable disease, defined as one the following: 1. Urine M-protein excretion ≥200 mg/24 h, or 2. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or 3. Free Light Chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (\<0.26 or \>1.65) only if patient has no measurable urine or serum M spike. * Patients with a history of Autologous Stem Cell Transplant (ASCT) are eligible for study participation provided the following eligibility criteria are met: 1. ASCT was \>100 days prior to the first dose of study medication, 2. No active bacterial, viral, or fungal infection(s) present. * 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 enrollment, except for alopecia. * Adequate organ system functions as defined by the laboratory assessments. * Contraceptive requirements for men and women per local regulations; strict pregnancy prevention for women of childbearing potential (WOCBP), including negative pregnancy tests and use of highly effective contraception. * Male participants must refrain from sperm donation and must use a condom plus an additional highly effective method of contraception if sexually active with a woman of childbearing potential. Specific Inclusion Criteria for BPd arm: • Prior treatment must include a lenalidomide-containing regimen, with lenalidomide administered for at least 2 consecutive cycles.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: Applicable for all (BPd, BVd, BKd): * Active plasma cell leukemia at Screening. * Symptomatic amyloidosis, including active Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma proliferative disorder, and Skin changes (POEMS). * Previous or concurrent invasive malignancy other than MM, except: 1. The disease must be considered medically stable for at least 2 years; or 2. The patient must not be receiving active therapy, other than hormonal therapy for this disease. * Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment. * Plasmapheresis within 7 days prior to the first dose of study intervention. * Patients after prior allogeneic stem cell transplant * Any major surgery within 4 weeks prior to start of treatment, except for bone stabilizing surgery. * Evidence of active mucosal or internal bleeding. * Intolerance or contraindications to anti-viral prophylaxis. * Current corneal epithelial disease except for mild punctate keratopathy. * Systemic anti-myeloma therapy (including chemotherapy and systemic steroids); prior treatment with an anti-MM monoclonal antibody drug within 30 days of receiving the first dose of study intervention. * Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant's safety). Patients with isolated proteinuria resulting from MM are eligible, provided they fulfill certain criteria * Received prior B-cell maturation antigen (BCMA)-targeted therapy. * Contact lenses are prohibited while receiving belantamab mafodotin treatment. Use may be restarted after a qualified eye care specialist confirms there are no other contraindications. Bandage contact lenses are permitted during study treatment as directed by the treating eye care specialist. * HIV infection unless well-controlled, no recent AIDS-defining infections, and adequate CD4+ count. * Significant liver dysfunction (ALT \>2.5x ULN, bilirubin \>1.5x ULN, cirrhosis, unstable liver/biliary disease). * Positive hepatitis B or C markers unless criteria for resolved infection are met. * Evidence of cardiovascular risk including any of the following: untreated arrhythmias, recent MI/ACS/angioplasty/bypass, NYHA III/IV heart failure, uncontrolled hypertension, QTc prolongation. Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to approximately 52 months | ORR is defined as the percentage of participants with a confirmed partial response \[PR\] or better (i.e., PR, very good partial response (VGPR), complete response \[CR\], stringent complete response \[sCR\]). Responses will be assessed using International Myeloma Working Group (IMWG) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | Up to approximately 52 months | CRR is defined as the percentage of participants with a confirmed CR or better (i.e., CR, sCR). |
| Minimal Residual Disease (MRD) Negativity Rate | Up to approximately 52 months | MRD negativity rate is defined as the percentage of participants who achieve MRD negative status (as assessed by Next generation sequencing \[NGS\] at 10\^-5 threshold) at least once during the time of confirmed CR or better response as per IMWG. |
| Duration of Response (DoR) | Up to approximately 52 months | DoR is defined as the time from first documented evidence of PR or better until PD or death due to any cause. |
| Number of participants with adverse events (AEs), Serious adverse events (SAEs) by severity | Up to approximately 52 months | — |
| Number of participants with AEs leading to dose modifications or AEs leading to treatment discontinuation | Up to approximately 52 months | — |
| Number of Participants With Ocular Findings on Ophthalmic Examination by severity | Up to approximately 52 months | — |
| Proportion of participants showing concordance between patient-reported ocular symptoms and ophthalmic examination findings | Up to approximately 52 months | Ophthalmic examination findings will be summarized, and contingency table will be constructed to assess the concordance between the results from patient questionnaires (Ocular Surface Disease Index \[OSDI\], PRO-CTCAE ocular scale, and PROSIM-Q) and findings from clinician assessments (CTCAE for eye disorders and Keratopathy and Visual Acuity \[KVA\] grading scale). The proportion of participants showing concordance will be calculated from this analysis. |
Countries
France, Germany, Greece, Japan, Netherlands, South Korea, Spain, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed