Overview

Isatuximab in Combination With Rd Compared to Rd in Elderly Patients (Aged ≥70 Years) With NDMM

Status:
Recruiting
Trial end date:
2028-12-01
Target enrollment:
0
Participant gender:
All
Summary
As optimal tolerance is the key for developing new treatments for the very elderly population, the aim of the study is to compare the efficacy and tolerance of isatuximab in combination with lenalidomide+dexamethasone (Rd) versus Rd only in very elderly patients aged 70 years or older. ln sum, a clear and clinically highly relevant benefit is expected with the isatuximab-based triple combination compared to the standard Rd doublet.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators:
Assign Data Management and Biostatistics GmbH
Medical University of Vienna
Sanofi
University of Navarra
WiSP GmbH
Treatments:
Dexamethasone
Lenalidomide
Criteria
Inclusion Criteria:

- Age ≥ 70 years

- Able to provide written informed consent in accordance with federal, local, and
institutional guidelines

- Patients must have newly diagnosed, symptomatic multiple myeloma with evidence of
measurable disease (assessed within 21 days prior to randomization)

- Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis
and/or

- Urine M protein ≥200 mg/24 hours measured using urine protein
immunoelectrophoresis and/or

- In subjects without detectable serum or urine M-protein, serum-free light chain
(SFLC) ≥100 mg/L (involved light chain) and an abnormal FLC ratio

- No prior treatment for multiple myeloma

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2

- Patients at cardiac risk (NYHA >ll) or pre-existing coronary heart disease, or any
other clinically relevant cardiac complication) should be scheduled for a baseline
ECHO and can only be included if the LVEF is >40%

- Adequate organ and bone marrow function within the 21 days prior to randomization
defined by:

- Bilirubin < 2 times the upper limit of normal (ULN), Aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) < 3 times the ULN

- absolute neutrophil count (ANC) ≥ 750/mm3 (growth factor support for max 3 days
allowed to achieve this value)

- Hemoglobin >8.0 g/dL (Use of erythropoietic stimulating factors and red blood
cell [RBC] transfusion per institutional guidelines is allowed, however the most
recent RBC transfusion may not have been done within 7 days prior to obtaining
screening hemoglobin.)

- Platelet count >50,000/mm3

- Calculated or measured creatinine clearance (CrCl) of ≥30 mL/min; Calculation
should be based on the MDRD formula (age, gender, black/non- black, weight,
height)

Exclusion Criteria:

- ECOG status >2

- Patients unlikely to tolerate Rd

- Waldenström macroglobulinemia

- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes)

- Plasma cell leukemia (> 2.0 x 10^9/L circulating plasma cells by standard
differential)

- Myelodysplastic syndrome

- Smoldering Myeloma and MGUS

- Second malignancy within the past 5 years except:

- Adequately treated basal cell or squamous cell skin cancer

- Carcinoma in situ of the cervix

- Prostate cancer ≤ Gleason score 6 with stable prostate-specific antigen (PSA over
12 months)

- Ductal breast carcinoma in situ with full surgical resection (i.e., negative
margins)

- Treated medullary or papillary thyroid cancer

- History of or current amyloidosis

- Glucocorticoid therapy within the 14 days prior to randomization that exceeds an
accumulated dose of 160 mg dexamethasone or 1000 mg prednisone

- Extended field radio therapy (more than 3 fields) within the 21 days prior to
randomization

- Contraindication to isatuximab, dexamethasone, lenalidomide or any of the required
concomitant drugs or supportive treatments, including hypersensitivity to antiviral
drugs

- Active congestive heart failure (New York Heart Association [NYHA] Class III or IV),
symptomatic ischemia, conduction abnormalities uncontrolled by conventional
intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or
myocardial infarction within 4 months prior to enrolment

- Active infection within the 14 days prior to randomization requiring systemic
antibiotics and/or antiviral therapy

- Uncontrolled hypertension or uncontrolled diabetes despite medication

- Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days
prior to randomization

- Known cirrhosis

- Known human immunodeficiency virus (HIV) seropositivity or active hepatitis C or
hepatitis B infection (subjects with past hepatitis B virus [HBV] infection or
resolved HBV infection defined as having a negative HBsAg test and a positive antibody
to hepatitis B core antigen [anti HBc] antibody test are eligible; subjects positive
for hepatitis C virus [HCV] antibody are eligible only if polymerase chain reaction
[PCR] is negative for HCV RNA.)

- Participation in another interventional study within the 28 days prior to
randomization

- Major surgery (except kyphoplasty) within the 28 days prior to randomization

- Any other clinically significant medical disease or social condition that, in the
Investigator's opinion, may interfere with protocol adherence or a subject's ability
to give informed consent, be compliant with study procedures, or provide accurate
information.