This study is testing whether a lower dose of belantamab mafodotin used together with pomalidomide and dexamethasone can provide similar effectiveness with fewer side effects compared with the standard dose in patients with relapsed or refractory multiple myeloma.
Participants will be randomly assigned to receive either a reduced dose or a standard dose of belantamab mafodotin in combination with pomalidomide and dexamethasone. The study will evaluate treatment response, side effects, and minimal residual disease (MRD), which is a measure of the number of myeloma cells that remain after treatment. The goal is to determine whether treatment can be optimized while maintaining disease control and reducing treatment-related toxicity.
Inclusion Criteria:
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the REBEL study protocol.
Male or female, 18 years or older (at the time consent is obtained).
Have a confirmed diagnosis of MM as defined by the IMWG criteria.
Eastern Cooperative Oncology Group performance status of 0-2.
Have been previously treated with at least 1 prior line of MM therapy, including a lenalidomide-containing regimen (lenalidomide must have been administered for at least 2 consecutive cycles), and must have documented disease progression during or after their most recent therapy.
Must have at least ONE aspect of measurable disease, defined as one the following:
Have undergone autologous stem cell transplant (autoSCT) or are considered transplant ineligible. Participants with a history of autoSCT are eligible for study participation provided the following eligibility criteria are met:
All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events v5.0) must be Grade ≤1 at the time of enrolment, except for alopecia and Grade ≤ 2 peripheral neuropathy.
Compliance with contraceptive precautions in accordance with the protocol.
Organ System Function - adequate organ system functions as defined by the laboratory assessments
Hematologic:
Hepatic:
Renal o eGFR ≥30 mL/min/1.73 m2 (as calculated by MDRD formula)
Exclusion Criteria:
Active plasma cell leukemia, amyloidosis, POEMS syndrome, allogeneic SCT or currently active GvHD.
Anti-MM therapy or use of an investigational drug within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; Prior treatment with a monoclonal antibody drug within 30 days of receiving the first dose of study drugs.
Plasmapheresis within 7 days prior to the first dose of study drug.
Prior treatment with pomalidomide and belantamab mafodotin in any treatment line.
Evidence of cardiovascular risk including: current clinically significant (CS) untreated arrhythmias (eg. CS ECG abnormalities, 2nd degree (Mobitz Type II) or 3rd degree AV block); history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening; heart failure NYHA III or IV class; uncontrolled hypertension.
Any major surgery within the last 4 weeks.
Any other active malignancy, except the disease is medically stable for at least 2 years or not require active therapy other than hormonal.
Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin, drugs chemically related, or any of the components of the study treatment.
Evidence of active mucosal or internal bleeding.
Cirrhosis or current unstable liver or biliary disease assessed by Investigator. Stable non-cirrhotic chronic liver disease is acceptable if other entry criteria are met.
Intolerance or contraindications to anti-viral prophylaxis.
Active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrollment.
Known HIV infection, unless the participant can meet all of the following criteria:
Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of the study intervention, unless the participant can meet the following criteria:
Participants with hepatitis B will be excluded unless the patient is:
Presence of active serious renal conditions (e.g., requiring dialysis or any other condition that could affect the participant's safety). Isolated proteinuria due to MM is acceptable if other criteria are fulfilled.
Ongoing Grade 3 or higher peripheral neuropathy or neuropathic pain
Active or history of venous thromboembolism within the past 3 months.
Contraindications to anti-thrombotic prophylaxis.
Current corneal disease except for mild punctate keratopathy.
Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (also lab abnormalities) that could interfere with participant's safety, obtaining ICF or compliance to the study procedures.
Pregnant or lactating female.
krzysztof.jamroziak@wum.edu.pl
Participants receive a reduced-dose regimen of belantamab mafodotin administered intravenously in combination with pomalidomide and dexamethasone. Belantamab mafodotin is administered at 2.5 mg/kg in Cycle 1 and 1.9 mg/kg thereafter according to the protocol-defined schedule. Pomalidomide is administered orally on Days 1-21 of each 28-day cycle, and dexamethasone is administered orally once weekly. Participants may continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for discontinuation.
Participants receive a standard-dose regimen of belantamab mafodotin administered intravenously in combination with pomalidomide and dexamethasone. Belantamab mafodotin is administered at 2.5 mg/kg in Cycle 1 and 1.9 mg/kg every 4 weeks thereafter according to the protocol-defined schedule. Pomalidomide is administered orally on Days 1-21 of each 28-day cycle, and dexamethasone is administered orally once weekly. Participants may continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for discontinuation.
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