Belantamab Mafodotin in patients with relapsed or refractory AL amyloidosis

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2020-004001-32-NL
• Date of registration: 29/01/2021
• Prospective Registration: Yes
• Primary sponsor: European Myeloma Network – EMN
• Public title: Belantamab Mafodotin in patients with relapsed or refractory AL amyloidosis
• Scientific title: A phase 2 study of Belantamab Mafodotin in patients with relapsed or refractory AL amyloidosis
• Date of first enrolment: 24/06/2021
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004001-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Greece, Italy, Netherlands, United Kingdom

Contacts

• Name: EMN
• Affiliation: European Myeloma Network - EMN

• Name: EMN
• Affiliation: European Myeloma Network - EMN

Key inclusion & exclusion criteria

Inclusion criteria:
1.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.
2.Patients must have had at least two cycles of therapy directed against plasma cell clone. However, patients that have received high dose therapy with melphalan as their only therapy are also eligible.
3.Patients must be 18 years of age or above.
4.ECOG performance status 0, 1 or 2.
5.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)
6.Supine systolic blood pressure = 90 mmHg.
7.Measurable disease defined by at least one of the following:
a.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).
b.presence of a monoclonal spike that is =0.5 g/dl.
8.Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system).
9. Patients must have adequate organ function.
10.Written informed consent in accordance with local and institutional guidelines.
11.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 breast-feeding, and at least one of the following conditions applies:
a.She is not of childbearing potential (WOCBP)
OR
b.She is a WOCBP and using, during the intervention period and for at least 4 months after the last dose of the study, a contraceptive method that is highly effective (failure rate <1% per year), preferably with low user dependency (as described in Appendix 3). Patient 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) 72 hours before the first dose of the study intervention.
The investigator is responsible for reviewing the 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):
a.=45 years of age and has not had menses for >1 year
b.Patients who have been amenorrhoeic for <2 years without a history of hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range after screening evaluation
c.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.
12. 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 part
Exclusion criteria:
1.Presence of non-AL amyloidosis.
2.Presence of lytic bone lesions or active myeloma with hypercalcemia, cast nephropathy, anemia due to marrow infiltration or extramedullary disease > 60% plasma cells in bone marrow.
3.Previous exposure to anti-BCMA agents.
4.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.
5.Known repetitive ventricular arrhythmias on 24h Holter Electrocardiograms (ECG) despite anti-arrhythmic treatment. Patient 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, electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities (unless patient has a pacemaker).
•Uncontrolled hypertension or hypotension (i.e., supine SBP< 90 mmHg despite supportive therapy with midodrine)
6.Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to Cycle 1 Day 1.
7.Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to Cycle 1 Day 1.
8.Ongoing corneal epithelial disease except mild changes in corneal epithelium.
9.Current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia (except due to 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 of malignancy is acceptable if otherwise meets entry criteria.
10.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.
11.Patient must not use contact lenses while participating in this study.
12.Patient must not be simultaneously enrolled in any interventional clinical trial.
13.Use of an investigational drug or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or five half-lives, whichever is shorter, prior to the first dose of study drug.
14.Plasmapheresis within seven days prior to the first dose of the study treatment.
15.Treatment with a monoclonal antibody within 30 days prior to the first dose of the study treatment. Serious conditions unrelated to AL, such as SARS-CoV-2, may be permitted but need to be discussed with the medical doctor and study-site personnel.
16.Major surgery = 4 weeks prior to initiating study treatment.
17.Evidence of active mucosal or internal bleeding
18.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.
19.Active infection requiring treatment.
20.Kn

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed or refractory AL amyloidosis
MedDRA version: 20.0 Level: PT Classification code 10002022 Term: Amyloidosis System Organ Class: 10021428 - Immune system disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: belantamab mafodotin
Product Code: GSK2857916
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: belantamab mafodotin
CAS Number: 2050232-20-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To evaluate the efficacy of blmf in patients with relapsed or refractory AL amyloidosis.

Primary end point(s): The primary end point of the study is the CR/VGPR/low-dFLC response rate at 6 months/ 4 cycles from start of therapy with blmf, according to consensus response criteria

Secondary Objective: 1.The safety of blmf in patients with relapsed or refractory AL amyloidosis.
a.Rates of AEs grade 3 or higher, related to blmf therapy
b.Rates of treatment discontinuation due to toxicity related to blmf
c.Dose reduction due to toxicity of blmf therapy
d.Any grade hematologic AEs
e.Any grade non-hematologic AEs
f.Rates of AEs of special interest
2.Secondary efficacy evaluations:
a.Overall hematologic response rates
b.Organ response rates per individual organ
c.Time to first hematologic response
d.Time to at least a very good hematologic response
e.Time to at least a low-dFLC response
f.Duration of hematologic response (time from first response to hematologic progression, for those who achieved at least a hematologic PR or low-dFLC response)
g.Time to a subsequent therapy, either due to progression or inadequate response
h.Time to hematologic progression or major organ deterioration or death
i.Overall survival
j.Quality of life
3. Characterization of the blmf PK profile

Timepoint(s) of evaluation of this end point: At 6 months/ 4 cycles from start of therapy with blmf

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: for the entire duration of the study

Secondary end point(s): •Evaluation of safety (grade 3 or higher adverse events rates related to blmf therapy, treatment discontinuation rates, any grade hematologic adverse events, any grade non-hematologic adverse events) and
•Further evaluation of efficacy (Overall hematologic response rates at 6 months (CR+VGPR+low-dFLC response+ PR), Organ response rates per individual organ (heart, kidney, liver) at 3, 6, 12, 18 and 24 months from start of therapy, Time to first hematologic response (PR or better), Time to at least a very good hematologic response (VGPR or better), Time to at least a low-dFLC response, Duration of hematologic response (time from first response to hematologic progression, for those who achieved at least a hemPR or low-dFLC response), Time to a subsequent therapy, either due to progression or inadequate response, Time to hematologic progression or major organ deterioration or death, overall survival and quality of life))"
•Derived PK parameter values for belantamab mafodotin as data permit.
Exploratory Endpoints:
•Relation between baseline bone marrow BCMA expression levels/soluble BCMA (sBCMA) levels AND clinical response.
•Change from baseline of sBCMA levels.

Secondary ID(s)

2020-004001-32-FR

EMN27

Source(s) of Monetary Support

GlaxoSmithKline Research and Development Ltd

Ethics review

Status: Approved
Approval date: 24/06/2021
Contact: