DREAMM-14 - A Phase II study to investigate alternative dosing regimens of Belantamab-Mafodotin as a monotherapy (GSK2857916) in relapsed or refractory multiple myeloma
Descrizione riassuntiva dello studio
In patients with worsening multiple myeloma (so-called relapsed/refractory multiple myeloma), the drug Belantamab-Mafodotin (Blenrep) has been approved for treatment in some countries, including Switzerland. Belantamab-Mafodotin is an antibody-drug combination (also known as antibody-drug conjugate, abbreviated ADC). Antibodies are natural substances that the body produces to fend off infections. ADCs are manufactured in the laboratory and are designed to deliver toxins (harmful substances) specifically to certain cancer cells to damage them while limiting damage to healthy cells. The B-cell maturation antigen (BCMA) is a protein that may be present on the surface of cancer cells in multiple myeloma. Belantamab-Mafodotin is targeted at the BCMA protein to locate and destroy myeloma cancer cells. However, in some individuals who have received Belantamab-Mafodotin in clinical trials, problems in the front part of the eye, the cornea, have occurred. This has led to symptoms such as dry eyes and blurred vision. These symptoms usually resolve when the study drug is paused for a period of time and the dose is lowered upon re-administration. Generally, participants continued to derive benefit from the study treatment. In our research project, we therefore want to find out: 1. whether a lower dose of Belantamab-Mafodotin (and/or a greater interval between doses) causes fewer eye-related complaints than the already approved dose of 2.5 mg/kg every three weeks; and 2. whether this lower dose (and/or greater interval between doses) is as effective in treating multiple myeloma as the approved dose. All treatment groups will receive Belantamab-Mafodotin, but with different dosing regimens.
(BASEC)
Intervento studiato
All study participants will be randomly assigned to treatment groups using a computer. This is called randomization. Neither you nor your investigator can decide which group you will be assigned to, and the assignment cannot be changed. This is an "open-label" study. This means that you, the investigator, and the study staff know which treatment group you have been assigned to and what treatment you are receiving.
Study participants will be divided into five groups (Group A, B, C, D, and E) and all will receive the study medication Belantamab-Mafodotin, but with different dosing regimens. The groups differ in the dose of the administered medication and the intervals between doses. In Group A, the approved dose of Belantamab-Mafodotin of 2.5 mg/kg will be administered every three weeks. In Groups B-E, either a lower dose of 1.9 mg/kg will be administered and/or with longer intervals between doses of up to 6 weeks.
(BASEC)
Malattie studiate
Relapsed or refractory multiple myeloma. Multiple myeloma is a type of bone marrow cancer. Bone marrow is the spongy tissue in the center of some bones that produces the body's blood cells. In multiple myeloma, the antibody-producing cells (called plasma cells) of the bone marrow multiply. Relapsed or refractory means that there is a recurrence and worsening of multiple myeloma after the disease has already been treated for this reason.
(BASEC)
All individuals with a confirmed diagnosis of multiple myeloma are eligible to participate, provided that the following criteria are met: • The disease has worsened or recurred after having been previously treated for this reason (refractory/relapsed). At least three prior lines of therapy have failed, including a so-called anti-CD38 antibody alone or in combination, an immunomodulator (a drug that affects the immune system), and a proteasome inhibitor (an inhibitor of a cellular subunit). • An autologous stem cell transplant has been performed more than 100 days ago or an autologous stem cell transplant could not be performed. • Patients are 18 years of age or older and consent to participate in the study. (BASEC)
Criteri di esclusione
However, individuals are not allowed to participate if they: • have symptomatic amyloidosis, active POEMS syndrome (a rare blood disorder), or active plasma cell leukemia at the time of the pre-study examination (screening) or have had it in the past. • have had prior treatment with a targeted therapy against the B-cell maturation antigen (BCMA). • have active kidney disease, corneal disease, or another malignant disease (except for diseases from which the participant has been disease-free for > 2 years). (BASEC)
Luogo dello studio
Berna
(BASEC)
Sponsor
GlaxoSmithKline AG
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Prof. Dr. med. Thomas Pabst
+41 31 632 84 30
thomas.pabst@clutterinsel.chInselspital Bern
(BASEC)
Informazioni generali
GlaxoSmithKline
(ICTRP)
Informazioni scientifiche
GlaxoSmithKline
(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica Berna
(BASEC)
Data di approvazione del comitato etico
22.11.2022
(BASEC)
ID di studio ICTRP
NCT05064358 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 2, Randomized, Parallel, Open-Label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Various Dosing Regimens of Single-Agent Belantamab Mafodotin (GSK2857916) in Participants with Relapsed or Refractory Multiple Myeloma (DREAMM-14) (BASEC)
Titolo accademico
A Phase 2, Randomized, Parallel, Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Various Dosing Regimens of Single-agent Belantamab Mafodotin (GSK2857916) in Participants With Relapsed or Refractory Multiple Myeloma (DREAMM-14) (ICTRP)
Titolo pubblico
Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple Myeloma (ICTRP)
Malattie studiate
Multiple Myeloma (ICTRP)
Intervento studiato
Drug: Belantamab mafodotin (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
Inclusion Criteria:
- Participant must be 18 years of age inclusive at the time of signing the informed
consent form (ICF).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Histologically or cytologically confirmed diagnosis of MM and a. Has undergone stem
cell transplant or is considered transplant ineligible, and b. Has failed at least 3
prior lines of anti-myeloma therapies, including an anti-cluster of differentiation
(CD)38 antibody (e.g., daratumumab) alone or in combination and is refractory to an
immunomodulatory agent (e.g., lenalidomide, pomalidomide) and a proteasome inhibitor
(e.g., bortezomib, ixazomib, carfilzomib).
- France specific: participants have failed at least 4 prior lines of anti-myeloma
therapies
- Participant has measurable disease per modified IMWG criteria.
- Life expectancy of at least 6 months, in the opinion of the investigator.
- Male and female participants agree to abide by protocol-defined contraceptive
requirements.
- Participant is capable of giving signed informed consent.
- Participant meets country-specific inclusion criteria described in the protocol.
Exclusion Criteria:
- Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, myeloma protein, and skin changes), or active plasma cell leukemia
at the time of screening.
- Current corneal epithelial disease, except nonconfluent superficial punctate
keratitis (SPK).
- Evidence of active mucosal or internal bleeding.
- Presence of an active renal condition.
- Any serious and/or unstable pre-existing medical condition, psychiatric disorder, or
other conditions that could interfere with the participant's safety, obtaining
informed consent, or compliance with the study procedures.
- Malignancies other than the disease under study, except for any other malignancy
from which the participant has been disease free for >2 years and, will not affect
the evaluation of the effects of the study treatment on the currently targeted
malignancy (MM). Participants with curatively treated non-melanoma skin cancer may
be enrolled without a 2-year restriction.
- Evidence of cardiovascular risk as per the protocol criteria.
- Pregnant or lactating female.
- Active infection requiring antibiotic, antiviral, or antifungal treatment.
- Known human immunodeficiency virus (HIV) infection, unless the criteria in protocol
can be met.
- Hepatitis B and C will be excluded unless the criteria in protocol can be met.
- Cirrhosis or current unstable liver or biliary disease.
- Alanine aminotransferase (ALT) >2.5 upper limit of normal (ULN).
- Total Bilirubin >1.5ULN.
- Systemic anti-MM therapy within <=14 days or 5 half-lives, whichever is shorter.
- Systemic therapy with high dose steroids within <=14 days before the first dose of
study treatment.
- Prior allogenic stem cell transplant.
- Prior treatment with a monoclonal antibody <=30 days before the first dose of study
treatment. Use of monoclonal antibodies for serious conditions unrelated to multiple
myeloma, such as COVID, may be permitted.
- Prior treatment with an anti-B cell maturation antigen (BCMA) targeted therapy or
hypersensitivity reactions to any components of the study treatment.
- Treatment with an antibody-drug conjugate.
- Participant has received any major surgery <=4 weeks before the first dose of study
treatment. An exception may be allowed for bone stabilizing surgery.
- Inadequate bone marrow reserve or organ functions as demonstrated by any of the
following: a. Absolute neutrophil count <1.010^9/L, b. Hemoglobin <8 gram/deciliter
(g/dL), c. Platelet count <5010^9/L, d. Spot urine (albumin/creatinine ratio) >500
milligram/gram (mg/g), e. Estimated glomerular filtration rate (eGFR) <30 milliliter
per minute per 1.73 meter square (mL/min/1.73m^2).
- UK specific: a. Absolute neutrophil count <1.510^9/L, c. Platelet count <7510^9/L (ICTRP)
non disponibile
Endpoint primari e secondari
Incidence rate of Grade =2 Corneal events according to the keratopathy visual acuity (KVA) scale (ICTRP)
Cumulative event rate of corneal events to Week 16 (KVA scale);Incidence rate of corneal events by grade (KVA scale);Exposure adjusted incidence rate of corneal events by grade (KVA scale);Median duration of dose delay;Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to corneal events;Cumulative incidence of corneal events by grade;Toxicity Index score by assessment/visit;Duration of corneal events;Percentage of time on study with corneal events;Change in best corrected visual acuity (BCVA);Overall response rate (ORR);Percentage of participants with very good partial response (VGPR) or better;Time to response (TTR);Duration of response (DoR);Time to progression (TTP);Progression-free survival (PFS);Overall survival (OS);Number of participants with AEs and serious AEs (SAEs);Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis laboratory parameters;Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to any AEs;Maximum concentration (Cmax) of belantamab mafodotin;Time taken to reach Cmax (Tmax) of belantamab mafodotin;Area under the concentration time-curve (AUC) of belantamab mafodotin;Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin;Titers of ADAs against belantamab mafodotin (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
GSK Clinical Trials, GlaxoSmithKline (ICTRP)
ID secondari
2021-004151-16, 2023-508213-16, 209628 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT05064358 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile