Comparing Lower Versus Standard Doses of Belantamab Mafodotin With Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma.

NCT07748689 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: PMC0122025-525096-83-00
• Study Type: interventional
• Target: 228
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Relapsed / Refractory Multiple Myeloma

Keywords

multiple myeloma; Relapsed/Refractory Multiple Myeloma; Belantamab Mafodotin; MRD-Guided Therapy; Measurable Residual Disease

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  Overall Response Rate (ORR), defined as the proportion of participants achieving at least a partial response according to International Myeloma Working Group (IMWG) response criteria.

  From randomization up to approximately 6 years

• Incidence of Grade 2 or Higher Ocular Toxicity

  Incidence of ocular toxicity of at least Grade 2 severity, assessed using the keratopathy and visual acuity (KVA) scale and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

  From randomization up to approximately 6 years

Secondary Outcomes (12)

• Incidence and Severity of Adverse Events

  From first study treatment dose up to approximately 6 years

• Undetectable Measurable Residual Disease (uMRD) Rate

  At 6, 12, 18, 24, 30, 36, and 42 months from randomization

• Sustained Undetectable Measurable Residual Disease (uMRD) Negativity Rate

  From randomization up to approximately 6 years

• Overall Response Rate (ORR)

  From randomization up to approximately 6 years

• Complete Response (CR) Rate

  From randomization up to approximately 6 years

Study Arms (2)

Arm A - Reduced-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone

EXPERIMENTAL

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.

Drug: Belantamab Mafodotin; Drug: Pomalidomide; Drug: Dexamethasone

Arm B - Standard-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone

ACTIVE COMPARATOR

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.

Drug: Belantamab Mafodotin; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Belantamab Mafodotin DRUG

Belantamab mafodotin is administered intravenously in combination with pomalidomide and dexamethasone. The study evaluates a reduced-dose strategy versus a standard-dose strategy of belantamab mafodotin in patients with relapsed or refractory multiple myeloma.

Arm A - Reduced-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone; Arm B - Standard-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone

Pomalidomide DRUG

Pomalidomide is administered orally in combination with belantamab mafodotin and dexamethasone. Participants receive pomalidomide according to the protocol-defined treatment regimen

Arm A - Reduced-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone; Arm B - Standard-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone

Dexamethasone DRUG

Dexamethasone is administered orally in combination with belantamab mafodotin and pomalidomide. Participants receive dexamethasone according to the protocol-defined treatment regimen

Arm A - Reduced-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone; Arm B - Standard-Dose Belantamab Mafodotin Plus Pomalidomide and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Urine M-protein excretion ≥200 mg/24 h, or
• Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or
• Serum 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 the patient has no measurable urine or serum M spike.
• 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:
• AutoSCT was \>100 days prior to the first dose of study medication
• No active bacterial, viral, or fungal infection(s) present
• 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

You may not qualify if:

• 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:
• Established ART for at least 4 weeks and HIV viral load \< 400 copies/mL within Screening Period.
• CD4+ T-cell (CD4+) counts ≥350 cells/μL.

Sponsors & Collaborators

• Polish Myeloma Consortium: lead
• Medical Research Agency, Poland: collaborator
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

belantamab mafodotin; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

Krzysztof Jamroziak, Professor

CONTACT

+48 22 599 29 41; krzysztof.jamroziak@wum.edu.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 6, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 1, 2033
• Study Completion (Estimated): March 1, 2033
• Last Updated: August 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share