AL AmyloidosisPhase 2EMN27NCT04617925
A Study of Belantamab Mafodotin in Patients With Relapsed or Refractory AL Amyloidosis
A Phase 2 study testing Belantamab mafodotin in people with AL Amyloidosis, run by Stichting European Myeloma Network at 6 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AL Amyloidosis
- What is being tested?
- Belantamab mafodotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 26 Feb 2021to 17 Jul 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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:
- Total bilirubin ≤1.5X ULN (Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) ALT ≤2.5 X ULN Renal: eGFR ≥30 mL/min/ 1.73 m2 Cardiac:LVEF (Echo) Clinically asymptomatic patients with ECHO confirmed LVEF ≥25%
- Written informed consent in accordance with local and institutional guidelines.
- Female patients: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP) OR
- Is a WOCBP and using a contraceptive method that is highly effective (failure rate of <1% per year), preferably with low user dependency (as described in Appendix 3), during the intervention period and for at least four months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
- A WOCBP must have a negative highly-sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
- Nonchildbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year,
- Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation,
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
- Male Patients : contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Male Patients are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm:
- Refrain from donating sperm
- PLUS either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
- OR
- Must agree to use contraception/barrier as detailed below: Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a WOCBP who is not currently pregnant.
- All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for AEs (NCI-CTCAE), version 5, corneal toxicities are defined according to the Keratopathy Visual Activity [KVA] scale) must be ≤ Grade 1 at the time of enrolment except for alopecia.
- Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent
Who cannot join
- 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:
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- 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.
- Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect the patient's safety) unrelated to AL amyloidosis. Patients with isolated proteinuria resulting from AL are eligible, provided they fulfil other inclusion criteria
- Patients must not use contact lenses while participating in this study.
- Patients must not be simultaneously enrolled in any interventional clinical trial.
- Use of an investigational drug or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
- Plasmapheresis within 7 days prior to first dose of study treatment.
- Treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
- Major surgery ≤ 4 weeks prior to initiating study treatment.
- Any evidence of active mucosal or internal bleeding.
- Known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to blmf or drugs chemically related to blmf, or any of the components of the study treatment.
- Active infection requiring treatment.
- Known HIV infection (defined by positive testing for human immunodeficiency virus (HIV) antibodies).
- Positive test of hepatitis B surface antigen, or hepatitis B core antibody at screening or within 3 months prior to first dose of study treatment.
- Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
- Note: Patients with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained.
- Note: Hepatitis RNA testing is optional and patients with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
- Invasive malignancies other than disease under study, unless the second malignancy has been medically stable for at least 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy. Patients with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction.
- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with the patient's safety, obtaining informed consent or compliance to the study procedures.
- Patients must not be pregnant or breast-feeding
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
About this study
Official title: A Phase 2 Study of Belantamab Mafodotin in Patients With Relapsed or Refractory AL Amyloidosis
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.
Read more
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
- Being tested
- Belantamab mafodotin
- Keywords
- Belantamab mafodotin
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belantamab mafodotinDrug
Belantamab mafodotin will be administered as a monotherapy intravenously at a 2.5 mg/kg calculated dose
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Belantamab mafodotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at 6 months (cycle 4)
Secondary outcomes (11)
Adverse events
Rates of grade 3 or higher AEs related to blmf therapy
Measured: up to 70 days after last dose
Treatment discontinuation
Rates of treatment discontinuation due to toxicity related to blmf
Measured: up to 1 year
Dose reduction
Dose reduction due to toxicity of blmf therapy
Measured: up to 1 year
Hematologic AEs
rates of any hematologic adverse events
Measured: up to 70 days after last dose
Non-hematologic AEs
rates of any non-hematologic adverse events
Measured: up to 70 days after last dose
Ocular toxicity
rates of adverse events of special interest
Measured: up to 1 year
Overall hematologic response rates
Complete Response (CR)/ Very Good Partial Response (VGPR)/ <50 mg/L difference between involved minus uninvolved serum free lights chains (low-dFLC)/ Partial Response (PR)
Measured: 3 months, 6 months
Organ response rates
Organ response rates per individual organ (heart, kidney, liver) according to International Amyloidosis Consensus Criteria
Measured: 3,6,12,18, and 24 months
Duration of response
Duration of response is defined as the time between first documentation of response (achievement of at least a PR or lowdFLC response) and PD
Measured: approximately up to 9 years
Determine time to progression
From the date of registration to the date of first disease progression, major organ deterioration or death, whichever occurs first
Measured: approximately up to 9 years
Overall survival
Overall Survival, measured from the date of from randomization to the date the subject's death
Measured: approximately up to 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2020
- Study start26 Feb 2021
- Primary completion17 Jul 2025
- Study completion17 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stichting European Myeloma Network
- Sponsor type
- Research network
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04617925
- Sponsor's protocol ID
- EMN27
- Acronym
- EMN27
- Status last verified
- Jul 2026
- First submitted
- 20 Oct 2020
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Belantamab Mafodotin in Patients With Relapsed or Refractory AL Amyloidosis
- ClinicalTrials.gov ID
- NCT04617925
- Acronym / sponsor ID
- EMN27 / EMN27
- Conditions
- AL Amyloidosis
- Keywords
- Belantamab mafodotin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Stichting European Myeloma NetworkResearch network
- Collaborators
- GlaxoSmithKline
- Study start
- 26 Feb 2021 (actual)
- Primary completion
- 17 Jul 2025 (actual)
- Study completion
- 17 Jul 2025 (actual)
- First posted
- 5 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| belantamab mafodotin | Experimental | Drug: Belantamab mafodotinBelantamab 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- 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)
Key exclusion criteria (33 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belantamab mafodotinBelantamab mafodotin will be administered as a monotherapy intravenously at a 2.5 mg/kg calculated dose | Drug | belantamab mafodotin |
Primary outcome
response rate
Time frame: at 6 months (cycle 4)
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
11 secondary outcomes
Adverse events
Time frame: up to 70 days after last dose
Treatment discontinuation
Time frame: up to 1 year
Dose reduction
Time frame: up to 1 year
Hematologic AEs
Time frame: up to 70 days after last dose
Non-hematologic AEs
Time frame: up to 70 days after last dose
Ocular toxicity
Time frame: up to 1 year
Overall hematologic response rates
Time frame: 3 months, 6 months
Organ response rates
Time frame: 3,6,12,18, and 24 months
Duration of response
Time frame: approximately up to 9 years
Determine time to progression
Time frame: approximately up to 9 years
Overall survival
Time frame: approximately up to 9 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
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Amyloidosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belantamab mafodotin in people with AL Amyloidosis, run by Stichting European Myeloma Network at 6 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France, Germany, Greece, Italy, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response rate (time frame: at 6 months (cycle 4)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.