Belantamab Mafodotin in patients with relapsed or refractory AL amyloidosis

Phase 1

Conditions: relapsed or refractory AL amyloidosis
MedDRA version: 20.0Level: PTClassification code 10002022Term: AmyloidosisSystem Organ Class: 10021428 - Immune system disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2020-004001-32-GR

Lead Sponsor: European Myeloma Network – EM

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 36

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 breastfeeding, 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 participate i

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.Kno

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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