Recruiting

Phase 2

Belantamab Mafodotin, Cyclophosphamide, Bortezomib, DexamethasoneA Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Cyclophosphamide, Bortezomib, and Dexamethasone in Adult Participants With Newly Diagnosed Amyloid Light Chain (AL) Amyloidosis

Sponsor:

GlaxoSmithKline

Code:

NCT07224672

Conditions

Amyloidosis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Belantamab mafodotin

Cyclophosphamide

Bortezomib

Dexamethasone

Study Details

Brief summary:

The study aims to evaluate the efficacy and safety of belantamab mafodotin in combination with cyclophosphamide, bortezomib, and dexamethasone in adult participants with newly diagnosed (ND) AL amyloidosis .

Conditions

Amyloidosis

Study ID

NCT07224672

Start date

Jun 24, 2026

Status verified date

Jul, 2026

Completion date

Jan 12, 2033

Anticipated

Primary completion date

Jan 12, 2033

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion criteria:

Participant is at least 18 years of age or the legal age of consent
Has histologically confirmed newly diagnosed primary AL amyloidosis according to the following criteria:

Presence of an amyloid-related systemic syndrome as per consensus guidelines.
Positive amyloid staining by Congo red stain with green birefringence on polarized light microscopy in any tissue AND at least 1 of the following tests to confirm amyloid type as AL Characteristic appearance by electron microscopy or confirmatory immunohistochemistry or AL amyloidosis typing by mass spectrometric proteomic analysis of the amyloid deposits or amyloid-typing by immunofluorescence oEvidence of a monoclonal plasma cell proliferative disorder
Measurable clonal disease as defined by at least 1 of the following:

Serum monoclonal protein >=0.5 grams per deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation performed at central laboratory),
Involved serum FLC >=5.0 milligram per deciliter (mg/dL) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved light chain, FLC concentrations (dFLC) >=5 mg/dL.
Not considered candidate for high-dose chemotherapy with autologous stem cell transplantation (ASCT) as part of first line of therapy
Is willing to use adequate contraception.
Is capable of giving signed informed consent
Has an Eastern Cooperative Oncology Group performance status of 0, 1 or 2
Has adequate hematologic, hepatic and renal function

Exclusion criteria:

Has a previous or current diagnosis of plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome or symptomatic multiple myeloma (MM), as per International Myeloma Working Group criteria for MM including the presence of lytic bone disease , plasmacytomas, or clonal BM plasma cells >=60%.
Has Immunoglobulin M (IgM)-related AL amyloidosis.
Has any form of non-AL amyloidosis, including wild type or mutated (Transthyretin amyloidosis \[ATTR\]) amyloidosis.
Has evidence of significant cardiovascular (CV) conditions as specified below:

New York Heart Association (NYHA) classification IIIb or IV heart failure.
Heart failure that in the opinion of the investigator is caused by ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram \[ECG\] changes) or uncorrected valvular disease and not primarily due to AL amyloidosis cardiomyopathy.
In-participant admission to a hospital for unstable angina or myocardial infarction within the last 3 months prior to screening or percutaneous cardiac intervention with recent stent within last 3 months prior to screening or coronary artery bypass grafting within the last 3 months prior to screening
Participants with current evidence of clinically significant untreated arrhythmia(s), including clinically significant ECG abnormalities including second-degree (Mobitz Type II) or third-degree atrioventricular block.
Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator is indicated but not placed (participants who do have a pacemaker/implantable cardioverter-defibrillator are allowed on the study).
Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >450 millisecond (msec) or >480 msec for participants with bundle branch block. Participants who have a pacemaker may be included regardless of calculated QTc interval.
Supine systolic blood pressure <90 millimeters of mercury (mmHg), or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of >20 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion.
Uncontrolled hypertension.
Has Mayo stage 3B disease
Has a current corneal epithelial disease except for mild punctate keratopathy.
Has previous or concurrent malignancies other than AL amyloidosis, except for any other malignancy that has been considered medically stable for at least 2 yearsThe participant must not be receiving active therapy, other than hormonal therapy for this disease.
Has major surgery within 2 weeks prior to the first dose of study interventions or has not recovered fully from surgery.
Has any history of prior allogenic or autologous BM transplant or other solid organ transplant.
Has known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, cyclophosphamide, bortezomib, boron or mannitol
Has active infection or active bleeding.
Has intolerance or contraindications to antiviral prophylaxis.
Has known Human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria:

Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/milliliter (mL) Cluster of differentiation 4 plus (CD4+) T-cell (CD4+) counts >=350 cells/microliter.
No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months.
Has prior therapy for AL amyloidosis or MM, with the exception of 160 milligram (mg) dexamethasone (or equivalent corticosteroid) maximum exposure prior to enrollment.
Has received any live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin
Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of interventional medical research within 28 days before enrollment.
Has an alanine aminotransferase (ALT) value >2.5\*upper limit of normal (ULN) or >3\*ULN if hepatic involvement of AL amyloidosis
Has a total bilirubin value >1.5\*ULN
Has cirrhosis or current unstable liver or biliary disease per investigator assessment Has documented presence of Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb) at screening or within 3 months prior to the first dose of study intervention, unless HBV DNA is undetectable at screening and participant receives antiviral prophylaxis or treatment.
Has a positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention unless the following criteria are met:

RNA test negative.
Successful antiviral treatment (usually 8 weeks duration), followed by a negative Hepatitis C virus RNA test after a washout period of at least 4 weeks.
Chronic hepatitis B infection, with the presence of HBsAg and/or detectable hepatitis B virus deoxyribonucleic acid (HBV DNA), and hepatitis D co-infection, with hepatitis D antibody and/or RNA, within 3 months

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose optimization phase: Belantamab mafodotin dose level 1 + CyBorD

Adult participants with newly diagnosed amyloid light chain (AL) amyloidosis will receive Belantamab mafodotin dose level 1 in combination with CyBorD in dose optimization phase.

experimental: Dose optimization phase: Belantamab mafodotin dose level 2+ CyBorD

Adult participants with newly diagnosed AL amyloidosis will receive Belantamab mafodotin dose level 2 in combination with CyBorD in dose optimization phase.

experimental: Dose expansion phase: Belantamab mafodotin + CyBorD

Adult participants with newly diagnosed AL amyloidosis will receive belantamab mafodotin at selected dose level from dose optimization phase in combination with CyBorD in dose expansion phase.

Interventions

Belantamab mafodotin

Belantamab mafodotin will be administered

Cyclophosphamide

Cyclophosphamide will be administered

Bortezomib

Bortezomib will be administered

Dexamethasone

Dexamethasone will be administered

Primary outcome measure

Overall complete hematologic response (CHR) rate [ Time Frame: Up to approximately 24 months ]

Central Contacts and Locations

Central contacts

US GSK Clinical Trials Call Center

877-379-3718 GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

+44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations

GSK Investigational Site

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

US GSK Clinical Trials Call Center

877-379-3718 GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Centre

+44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com

Principal Investigator:

Shaji Kumar

More Information

Sponsor

GlaxoSmithKline

Last update posted

Jul 17, 2026

Last verified

Jul, 2026

Keywords

Amyloid light chain amyloidosis
Bortezomib
Cyclophosphamide
Dexamethasone

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by GlaxoSmithKline on 2026-07-17.