Evaluation of belantamab mafodotin plus drug combination in adult patients with newly diagnosed light chain amyloidosis

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What is this study about?

The study focuses on adults who have been newly diagnosed with amyloid light chain amyloidosis, a rare condition in which abnormal protein fragments build up in organs such as the heart, kidneys, or liver, leading to organ problems. The treatment being tested combines an antibody drug called belantamab mafodotin with three chemotherapy agents: cyclophosphamide, bortezomib, and dexamethasone. All four medicines are given by mouth, injection under the skin, or infusion into a vein according to a set schedule.

The purpose of the study is to see whether this combination can more effectively control the disease while remaining safe. Participants will receive the medication cycles over several months, with regular clinic visits for drug administration, blood tests, and eye examinations to watch for any side effects. The study follows each person from the start of treatment through a follow‑up period to observe how the disease responds.

Effectiveness will be judged mainly by the proportion of people who achieve a Complete Hematologic Response, meaning blood tests show no detectable disease activity. Additional assessments include improvement in the function of affected organs (heart, kidney, liver) and monitoring of eye health because the antibody can cause changes on the surface of the eye. Safety will be tracked by recording any unwanted events, changes in laboratory results, and any signs of the body forming antibodies against the new drug.

1 enrollment and baseline assessments

after signing the consent form, you will be assigned to the study group and undergo initial assessments. these include a medical history review, blood tests, and an eye examination to record baseline vision.

the eye examination checks the cornea and visual acuity to detect any pre‑existing problems before treatment starts.

2 first treatment cycle

you will receive belantamab mafodotin as an intravenous infusion. the dose is 1.9 mg per kilogram of body weight, given in a solution that is infused through a vein.

on the same day you will take cyclophosphamide tablets by mouth. each tablet contains 500 mg of the active substance.

you will receive an injection of bortezomib under the skin (subcutaneous use). the dose is 1.3 mg per square meter of body surface area.

you will also take dexamethasone tablets by mouth. each tablet provides a total of 40 mg of the medication.

3 repeated treatment cycles

the combination of belantamab mafodotin, cyclophosphamide, bortezomib, and dexamethasone will be given again in subsequent cycles according to the study schedule. each cycle follows the same pattern of oral tablets, subcutaneous injection, and intravenous infusion.

the exact interval between cycles is defined by the study protocol and will be explained by the study team.

4 safety monitoring and examinations

regular blood tests will be performed to monitor how your body is responding to the medications and to detect any side effects.

periodic eye examinations will be scheduled to assess corneal health and visual acuity, because the study tracks ocular findings as a safety measure.

any adverse events, such as symptoms or changes in laboratory results, will be recorded and evaluated throughout the trial.

5 completion of treatment and follow‑up

after the planned number of treatment cycles is completed, you will enter a follow‑up period. during this time, additional visits will be made to assess the durability of the treatment response and to continue monitoring safety.

follow‑up visits may include blood tests, eye examinations, and assessments of organ function, as defined by the study.

Who Can Join the Study?

  • You must be at least 18 years old (or the legal age to give consent in your country) when you sign the study consent form.
  • You must have a new diagnosis of AL amyloidosis that is confirmed by a tissue test showing amyloid deposits, a special stain called Congo red that appears green under polarized light, and lab evidence of an abnormal plasma cell (a type of blood cell) producing a single kind of protein.
  • Your blood tests must show a measurable amount of the abnormal protein, such as a serum protein level of 0.5 g/dL or higher, or a free light chain level of 5 mg/dL or higher with an abnormal kappa : lambda ratio, or a difference between involved and uninvolved light chains (dFLC) of at least 5 mg/dL.
  • You must not be planned to receive high‑dose chemotherapy with an autologous stem cell transplant (a procedure that uses your own stem cells) as the first line of treatment.
  • You must agree to use effective birth control during the study and for a period after treatment. This includes men agreeing not to donate sperm and women agreeing not to donate eggs, and following the specific timing for contraception described in the study protocol.
  • You must be able to understand the study information and sign the informed consent form.
  • Your overall health must allow an ECOG performance status of 0, 1, or 2 (a scale that measures how well you can carry out daily activities) with no recent worsening in the past two weeks.
  • Your recent lab results must show adequate organ function, including a white blood cell count (ANC) of at least 1.0 × 10⁹/L, a platelet count of at least 75 × 10⁹/L, liver tests within allowed limits (total bilirubin ≤1.5 times the normal upper limit and ALT ≤2.5 or ≤3 times normal depending on liver involvement), and kidney function (eGFR) of 30 mL/min/1.73 m² or higher.

Who Cannot Join the Study?

  • Having a diagnosis of POEMS syndrome (a condition with nerve problems, enlarged organs, hormone issues, abnormal protein, and skin changes) or having active multiple myeloma (a cancer of plasma cells) that includes bone damage, bone tumors, or a high level of abnormal plasma cells in the bone marrow.
  • Having IgM-related AL amyloidosis, a specific type of amyloidosis linked to the IgM protein.
  • Having any other type of amyloidosis that is not AL amyloidosis, such as ATTR amyloidosis (amyloidosis caused by a different protein).
  • Having serious heart or blood vessel problems as defined in the study protocol.
  • Having Mayo stage 3B disease, which indicates very advanced amyloidosis.
  • Having an active eye surface disease (corneal epithelial disease) that is more than mild, small spots on the eye.
  • Having other cancers besides AL amyloidosis, unless the other cancer has been stable without treatment for at least two years and you are not receiving active therapy (except hormone therapy for that cancer).
  • Having had major surgery within two weeks before the first study drug dose or not having fully recovered from surgery.
  • Having had a previous bone‑marrow transplant (allogenic or autologous) or any solid‑organ transplant.
  • Having a known immediate or delayed allergic reaction (hypersensitivity) or unusual reaction (idiosyncratic) to any of the study drugs (belantamab mafodotin, cyclophosphamide, bortezomib, dexamethasone) or related substances such as boron or mannitol.
  • Having a serious or unstable medical or mental health condition, or abnormal lab results, that could affect safety, the ability to give consent, or follow study procedures.
  • Having an active infection or active bleeding.
  • Being unable to tolerate or having a contraindication to antiviral preventive medication.
  • Having known HIV infection, unless you have been on antiretroviral therapy for at least four weeks, have a low viral load (<400 copies/mL), a CD4+ cell count of 350 or higher, and no serious AIDS‑related infections in the past year.
  • Having received any prior treatment for AL amyloidosis or multiple myeloma, except for a limited amount of dexamethasone (up to 160 mg) before entering the study.
  • Having received any live or weakened (live‑attenuated) vaccine within 30 days before the first dose of belantamab mafodotin.
  • Being enrolled in, or having participated in, another clinical trial with an investigational drug within 28 days before enrollment.
  • Having a liver enzyme level (ALT) more than 2.5 times the normal upper limit, or more than 3 times if the liver is affected by AL amyloidosis.
  • Having a total bilirubin level (a measure of liver function) more than 1.5 times the normal upper limit.
  • Having liver cirrhosis or unstable liver or bile‑duct disease, such as fluid buildup in the abdomen (ascites), brain changes from liver disease (encephalopathy), clotting problems (coagulopathy), low blood protein (hypoalbuminemia), enlarged veins in the esophagus or stomach (varices), or persistent yellowing of the skin (jaundice).
  • Having a positive test for hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) at screening or within three months before the first dose, unless special exceptions apply.
  • Having a positive hepatitis C antibody or RNA test at screening or within three months before the first dose, unless you have a negative RNA test after successful antiviral treatment and a wash‑out period of at least four weeks.
  • Having chronic hepatitis B infection (positive HBsAg or detectable HBV DNA) or hepatitis D co‑infection (positive hepatitis D antibody or RNA) within three months.
  • Having a known blockage that prevents urine from flowing normally.
  • Having an acute, widespread lung disease that also involves the lining around the heart (pericardial disease).
  • Having any form of urinary outflow obstruction.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name City Country Status
Theagenio Cancer Hospital of Thessaloniki Thessaloniki Greece
Hospital Universitario De Salamanca Salamanca Spain
Azienda Ospedaliera Universitaria Federico II Di Napoli Naples Italy
Hospital Universitario De Navarra Pamplona Spain

Other Sites

Site Name City Country Status
Fondazione IRCCS Policlinico San Matteo Pavia Italy
Alexandra Hospital Athens Greece
Hospital Clinic De Barcelona Barcelona Spain
Hospital Universitario Virgen De La Victoria Malaga Spain
Azienda Ospedaliero Universitaria Pisana Pisa Italy

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Greece Greece
Not yet recruiting
21.07.2026
Italy Italy
Not yet recruiting
21.07.2026
Spain Spain
Not yet recruiting
21.07.2026

Trial locations

Belantamab mafodotin is an antibody‑drug conjugate designed to find and attach to a protein on the abnormal plasma cells that cause AL amyloidosis. By binding to these cells, it helps the body’s immune system recognize and destroy them, aiming to reduce the disease‑causing proteins.

Dexamethasone is a steroid medication that reduces inflammation and weakens the immune response. In this study it is given to help control symptoms of amyloidosis and to support the activity of the other cancer‑fighting drugs.

Cyclophosphamide is a chemotherapy agent that interferes with the DNA of fast‑growing cells. It helps to kill the abnormal plasma cells that produce harmful light chains, working together with the other drugs to improve overall treatment effect.

Bortezomib works by blocking a cellular “recycling” system called the proteasome. This causes a buildup of proteins inside the abnormal plasma cells, leading them to die. It is a key part of the standard combination used for AL amyloidosis.

GSK5764227 is an experimental drug given by IV infusion. Its role in the trial is to test whether adding this new agent can provide extra benefit when combined with the standard regimen, although its exact mechanism is still being studied.

Light chain amyloidosis – Light chain amyloidosis is a condition where abnormal proteins called light chains build up as sticky deposits in various organs. These deposits can cause the affected organ to become stiff and function less efficiently. Over time, the amount of protein buildup may increase, leading to gradual worsening of organ performance. Commonly involved organs include the heart, kidneys, and liver, and the disease may spread to additional sites as it advances. Symptoms often develop slowly, reflecting the progressive nature of the protein accumulation. The disease course is marked by a steady increase in tissue involvement unless the underlying process is halted.

Trial ID:
2025-522803-60-00
Protocol code:
223963
NCT ID:
NCT07224672
Trial Phase:
Therapeutic exploratory (Phase II)

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