A phase 2 study of Belantamab Mafodotin in patients with relapsed or refractory AL amyloidosis

Phase 2

Conditions: AL amyloidosis
primary amyloidosis
10035227

Registration Number: NL-OMON54340

Lead Sponsor: Stichting European Myeloma Network (EMN)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 2

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.Written informed consent in accordance with local
and institutional guidelines. 10.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 trial, 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 trial 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 trial 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 regulat

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 (mild punctate keratopathy).
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 trial. 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 trial drug.
14.Plasmapheresis within seven days prior to the first dose of the trial
treatment. Serious conditions unrelated to AL, such as SARS-CoV-2, may be
permitted but need to be discussed with the medical doctor and trial-site
personnel. 15.Treatment with a monoclonal antibody within 30 days prior to the
first dose of the trial treatment 16.Major surgery <= 4 weeks prior to
initiating trial treatment. 17.Evidence of active mucosal or internal bleeding
18.Known immediate o

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoint: The primary end point of the study is the CR/VGPR/low-dFLC<br /><br>response rate at 6 months/4 cycles from start of therapy with blmf, according<br /><br>to consensus response criteria.<br /><br>Stratification Factors: This is a single arm study; no stratification is<br /><br>required for disposition to treatment arms</p><br>

Secondary Outcome Measures