Phase 2 study of daratumumab monotherapy in previously untreated patients with stage 3B light chain (AL) amyloidosis

Phase 2

Recruiting

• Conditions: light chain (AL) amyloidosis; 10035227

• Registration Number: NL-OMON54540
• Lead Sponsor: Stichting European Myeloma Network

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1. Men or women 18 years of age or older., 2. Diagnosis of amyloidosis, AL
type, based on:, a. Histopathological diagnosis of amyloidosis based on
detection by immunohistochemistry and polarizing light microscopy of green
bi-refringent material in Congo Red stained tissue specimens (excluding bone
marrow) or characteristic electron microscopy appearance, AND, b. Measurable
disease of amyloid light chain amyloidosis as defined by at least ONE of the
following: , - serum monoclonal protein >=0.5 g/dL by protein electrophoresis
(routine serum protein electrophoresis and immunofixation performed at local
lab), - 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). Serum FLCs will be measured using the Freelite
assay at a central laboratory., - Note: Measurable disease by Urine Bence-Jones
Proteinuria is not sufficient for study enrolment. , AND, c. Cardiac
involvement by AL amyloidosis according to consensus guidelines (See ATTACHMENT
3), 3. Mayo Stage 3B disease, defined as both A. increased cardiac troponin
(hsTnT >54 pg/ml) AND B. increased NT-proBNP >= 8500 pg/ml, 4. For subjects
with congestive heart failure, symptoms should be optimally managed and
clinically stable with no cardiovascular-related hospitalizations within 2
weeks prior to Cycle 1 Day 1, as assessed by the Principal Investigator. [See
also exclusion criteria 3], 5. Eastern Cooperative Oncology Group (ECOG)
Performance Status (PS) 0, 1,2 or 3 (ATTACHMENT 1), 6. Subject must have
pre-treatment clinical laboratory values meeting the following criteria during
the Screening Phase:, a. Absolute neutrophil count >=1.0 × 109/L;, b. Hemoglobin
level >=8.0 g/dL (>=5 mmol/L), c. Platelet count >=75 × 109/L; platelet
transfusions are NOT acceptable, d. Alanine aminotransferase level (ALT) <=2.5 x
ULN;, e. Aspartate aminotransferase (AST) <=2.5 x ULN, f. Total bilirubin level
<=1.5 × ULN, except for subjects with history of Gilbert Syndrome, in which case
direct bilirubin <= 2 × ULN, g. Estimated Glomerular Filtration Rate (eGFR) >=20
mL/min; Please note that the eGFR is measured by using the CKD-EPI equation ,
7. Women of childbearing potential must commit to either abstain continuously
from heterosexual sexual intercourse (if this is the preferred and usual
lifestyle of the subject) or to use 2 methods of reliable birth control
simultaneously. This includes one highly effective form of contraception (tubal
ligation, intrauterine device, hormonal [birth control pills, injections,
hormonal patches, vaginal rings or implants] or partner*s vasectomy) and one
additional effective contraceptive method (male latex or synthetic condom,
diaphragm, or cervical cap). Contraception must begin prior to dosing and
continue for 3 months after discontinuation of daratumumab. Reliable
contraception is indicated even where there has been a history of infertility,
unless due to hysterectomy or bilateral oophorectomy., 8. During the study and
for 3 months after receiving the last dose of daratumumab, female subjects must
agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction., 9. A man who is sexually active with a woman of childbearing
potential and has not had a vasectomy

Exclusion Criteria

1.Prior therapy for AL amyloidosis or multiple myeloma with the exception of
160 mg dexamethasone (or equivalent steroid) maximum exposure prior to Cycle 1
Day 1., 2.Previous or current diagnosis of symptomatic multiple myeloma
including the presence of lytic bone disease, plasmacytomas, >= 60% plasma cells
in the bone marrow, and/or hypercalcemia., 3.Evidence of significant
cardiovascular conditions as specified below:, a. New York Heart Association
(NYHA) classification of heart failure, stages IIIB or IV , b. Heart failure
that in the opinion of the investigator due to ischemic heart disease or
uncorrected valvular disease, and not due to AL amyloid cardiomyopathy., c.
Hospitalization for unstable angina or myocardial infarction or percutaneous
cardiac intervention with recent stent or coronary artery bypass grafting, all
within the last 6 months prior to the first dose , d. Subjects with a history
of sustained ventricular tachycardia or aborted ventricular fibrillation or
with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal
dysfunction for which a pacemaker/ICD is indicated but will not be placed
(subjects who do have a pacemaker/ICD are allowed in the study), e. Screening
12-lead ECG showing a baseline QT interval as corrected by Fridericia*s formula
(QTcF) >500 msec. Subjects who have pacemaker may be included regardless of
calculated QTc interval., f. Supine systolic blood pressure <90 mmHg, or
symptomatic orthostatic hypotension, defined as a decrease in systolic blood
pressure upon standing of >20 mmHg despite medical management in the absence
of volume depletion, 4. Subjects planning to undergo a stem cell transplant
during the first 6 cycles of protocol therapy are excluded. Stem cell
collection during the first 6 cycles of protocol therapy is permitted., 5.
Diagnosed or treated for malignancy other than AL, except:, a. Malignancy
treated with curative intent and with no known active disease present for >=24
months before Cycle 1 Day 1, b. Adequately treated non-melanoma skin cancer or
lentigo maligna without evidence of disease, c. Adequately treated carcinoma in
situ (e.g. cervical, breast) with no evidence of disease, 6. Subject has known
chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in
1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required
for subjects suspected of having COPD and subjects must be excluded if FEV1
<50% of predicted normal, 7. Subject has known moderate or severe persistent
asthma within the past 2 years or currently has uncontrolled asthma of any
classification. (Note that subjects who currently have controlled intermittent
asthma or controlled mild persistent asthma are allowed in the study)., 8.
Subject is known to be seropositive for human immunodeficiency virus (HIV). HIV
positive subjects who are stable on highly active antiretroviral therapy
(HAART) with no opportunistic infections within the last 6 months are
eligible. , 9. Subjects known: a. To be seropositive for hepatitis B (defined
by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with
resolved infection (ie, subjects who are HBsAg negative but positive for
antibodies to hepatitis B core antigen [antiH-Bc] and/or antibodies to
hepatitis B surface antigen [anti-HBs]) mu

Study & Design

• Study Type: Interventional
• Study Design: Not specified