A Study of Belantamab Mafodotin in Patients With Relapsed or Refractory AL Amyloidosis

NCT04617925 | Completed Phase 2 DMC

• 1 other identifier: EMN27
• Study Type: interventional
• Target: 35
• Locations: 6 countries
• Sites: 6

Brief Summary

This is an open-label, multicenter, Phase 2 study in subjects with previously treated patients with light chain (AL) amyloidosis in need for therapy. Approximately 35 subjects will receive therapy with belantamab mafodotin. Subject participation will include a Screening Phase, a Treatment Phase, a Post-Treatment Observation Phase, and a Long-term Follow-up Phase. A safety run-in will be conducted in 6 subjects treated with belantamab mafodotin for at least 1 cycle. According to the two-stage statistical design of the study, an interim analysis of efficacy will occur. If after 15 patients have been enrolled at least 3 complete or very good partial responses have been recorded, the accrual will continue until all planned patients have been enrolled

Conditions

AL Amyloidosis

Keywords

Belantamab mafodotin

Outcome Measures

Primary Outcomes (1)

• response rate

  Complete Response (CR)/ Very Good Partial Response (VGPR)/ \<50 mg/L difference between involved minus uninvolved serum free lights chains (low-dFLC) according to the consensus recommendations for AL amyloidosis treatment response criteria

  at 6 months (cycle 4)

Secondary Outcomes (11)

• Adverse events

  up to 70 days after last dose

• Treatment discontinuation

  up to 1 year

• Dose reduction

  up to 1 year

• Hematologic AEs

  up to 70 days after last dose

• Non-hematologic AEs

  up to 70 days after last dose

Study Arms (1)

belantamab mafodotin

EXPERIMENTAL

Belantamab mafodotin will be administered as an IV infusion at a dose of 2.5 mg/kg every six weeks until progression of disease, unacceptable toxicity or subsequent therapy, for a maximum of eight doses (approximately 12 months), according to the response adapted modifications

Drug: Belantamab mafodotin

Interventions

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered as a monotherapy intravenously at a 2.5 mg/kg calculated dose

belantamab mafodotin

Eligibility Criteria

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

You may qualify if:

• Diagnosis of AL amyloidosis, confirmed by histology and typed with immunohistochemistry, immunoelectron microscopy or mass spectrometry or if not available, for patients with biopsy confirmed amyloidosis and cardiac involvement alone, if they also have a negative PYP- or DPD-Tc99m bone scan.
• Previous systemic therapy for AL amyloidosis
• Patients must be ≥ 18 years of age.
• ECOG performance status 0, 1 or 2.
• Mayo stage 1 or Mayo stage 2 or Mayo stage 3A1-3 defined as both cTnT \< 0.035 ng/mL (or in place of cTnT the cTnI \< 0.10 ng/mL or high sensitivity Troponin T \< 54 ng/L) AND simultaneous NT-proBNP ≤ 332 ng/L, OR EITHER above threshold, or BOTH above threshold but with NTproBNP \< 8500 ng/L (stage 3A disease)
• Supine systolic blood pressure ≥ 90 mmHg
• Measurable disease defined by at least one of the following:
• serum free light chain (FLC) ≥2.0 mg/dL (20 mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) ≥2mg/dL (20 mg/L).
• presence of a monoclonal spike that is ≥0.5 gr/dl.
• Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system).
• Patient must have adequate organ function, defined as follows:
• System Laboratory Values
• Hematologic:
• Absolute neutrophil count (ANC) ≥1.5 X 109/L Hemoglobin ≥8.0 g/dL Platelets ≥75 X 109/L
• Hepatic:

You may not qualify if:

• Presence of non-AL amyloidosis.
• Presence of lytic bone lesions or active myeloma with hypercalcemia, cast nephropathy, anemia due to marrow infiltration or extramedullary disease.
• Previously untreated disease: patients must have had at least 2 cycles of therapy directed against the plasma cell clone; however, patients that have received high dose therapy with melphalan as their only therapy are eligible for the study.
• Previous exposure to anti-BMCA agents
• Cardiac stage IIIB disease: both cTnT \> 0.035 ng/mL (or in place of cTnT the cTnI \> 0.10 ng/mL or high sensitivity Troponin T \> 54 ng/L) AND simultaneous NT-proBNP \>8500 ng/L.
• Known repetitive ventricular arrhythmias on 24h Holter Electrocardiogram (ECG) in spite of anti-arrhythmic treatment. Patients must not have evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block.
• History of myocardial infarction, acute coronary syndromes (including unstable or uncontrolled angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of Screening.
• Class III or IV heart failure as defined by the New York Heart Association functional classification system \[NYHA, 1994\]
• Severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless patient has a pacemaker.
• Uncontrolled hypertension or hypotension (i.e., supine SBPN \< 90 mmHg despite supportive therapy with midodrine)
• Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to Cycle 1 Day 1.
• Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to Cycle 1 Day 1.
• Current corneal epithelial disease except mild changes in corneal epithelium.
• Current unstable liver or biliary disease defined by the presence of large volume ascites requiring paracentesis, encephalopathy, coagulopathy, hypoalbuminemia (except due to AL related nephrotic syndrome), esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement due to AL amyloidosis is acceptable if otherwise meets entry criteria.

Sponsors & Collaborators

• Stichting European Myeloma Network: lead
• GlaxoSmithKline: collaborator

Study Sites (6)

Centre hospitalier Universitaire de Limoges -

Limoges, 87042, France

Location

University Hospital Heidelberg

Heidelberg, 69120, Germany

Location

General Hospital of Athens "Alexandra"

Athens, 115 28, Greece

Location

Fondazione I.R.C.C.S Policlinico "San Matteo"

Pavia, 27100, Italy

Location

UMC Utrecht

Utrecht, 3584 CX, Netherlands

Location

Royal Free Hospital - London,

London, United Kingdom

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

belantamab mafodotin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 5, 2020
• Study Start: February 26, 2021
• Primary Completion: July 17, 2025
• Study Completion: July 17, 2025
• Last Updated: September 5, 2025

Record last verified: 2025-09

Locations

NL (1); DE (1); IT (1); FR (1); GB (1); GR (1)