This study has been transitioned to CTIS with ID 2023-507143-11-00 check the CTIS register for the current data. Primary objective: To determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Reduction of risk to disease progression or death, instigated by daratumumab
treatment.
Assumption: Daratumumab treatment will reduce the risk of disease progression
or death by 37,5% with median PFS of 48 months for daratumumab compared to 30
months for active monitoring.
Secondary outcome
Not applicable
Background summary
Refer to question/answer C4.
Hypothesis: Daratumumab administered as monotherapy will prolong progression
free survival (PFS) compared with active monitoring in subjects with high-risk
SMM.
Study objective
This study has been transitioned to CTIS with ID 2023-507143-11-00 check the CTIS register for the current data.
Primary objective: To determine whether treatment with daratumumab administered
subcutaneously (SC) prolongs progression-free survival (PFS) compared to active
monitoring in subjects with high-risk smoldering multiple myeloma (SMM).
Secondary objectives:
# To demonstrate additional clinical benefit (overall response rate, duration
of response, overall survival, etc) for subjects with high-risk SMM treated
with daratumumab compared with active monitoring.
# To assess the safety profile of daratumumab in subjects with high-risk SMM.
# To assess the clinical characteristics of symptomatic multiple myeloma (MM)
following progression of disease after therapy with daratumumab
# To evaluate the pharmacokinetics and immunogenicity of daratumumab
administered SC in subjects with high-risk SMM.
# To evaluate the immunogenicity of recombinant human hyaluronidase (rHuPH20)
when administered in combination with daratumumab SC in subjects with high-risk
SMM.
# To evaluate the effect of treatment with daratumumab on health-related
quality of life.
Exploratory objectives
# To investigate clinical efficacy of daratumumab in high-risk subjects with
genetic modifications (del17p, t(4:14), 1q gain, or other high-risk molecular
subtypes).
# To explore biomarkers of response or resistance to daratumumab, including
immunophenotypes and expression of MM markers (ie, CD38).
Study design
Phase 3, randomized, open-label, 2-arm, multicenter study to evaluate the
efficacy and safety of daratumumab SC administration versus active monitoring
in subjects with high-risk SMM. Approximately 360 subjects will be assigned
randomly to active monitoring (Arm A) or daratumumab (Arm B) in a 1:1 ratio.
Intervention
Subjects randomized to active monitoring (arm A) will receive no study
medication, but will undergo the same disease evaluations and at the same
frequency as subjects randomized to daratumumab (arm B). Subjects randomized to
daratumumab will receive daratumumab 1800 mg administered by subcutaneous
injection once weekly in Cycle 1 and 2, then every 2 weeks for Cycle 3 to Cycle
6, and thereafter every 4 weeks for up to 36 months. Each cycle will be 28
days.
Study burden and risks
Burden (both arm A and B): Hospital visits on a more frequent schedule than
standard, including additional assessments.
Risks (arm B): Adverse Events observed mostly related to the IV administration
of daratumumab are fever, high protein levels in the urine, fatigue,
infusion-related reactions, diarrhea, cough, infection of the nose, sinuses
and/or throat, nausea, dizziness, colds and back pain (refer to the patient
information sheet for a complete overview). Adverse Events for daratumumab
administered SC appear to be similar to those reported in single-agent studies
of daratumumab administered IV, but with a lower incidence of
infusion/injection-related reactions (IRRs). The incidence of all-grade IRRs
was 13% and 24% in different dose cohorts. By comparison, among subjects
treated in single-agent or combination studies with IV daratumumab, IRRs were
reported in 47% of subjects. Administration of daratumumab in the abdominal SC
tissue was associated with injection site erythema in 34% of subjects and
induration 26% of subjects.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
# At least 18 years of age with an Eastern Cooperative Oncology Group (ECOG)
performance status score of 0 or 1
# Diagnosis of SMM for <=5 years with measurable disease (defined as serum M
protein >=10 g/L or urine M protein >=200 mg/24 hours or involved serum Free
Light Chain (FLC) >=100 mg/L and abnormal serum FLC ratio)
# Clonal Bone Marrow Plasma Cells (BMPCs) >=10% and at least 1 of the following:
*Serum M protein >=30 g/L and/or *IgA SMM and/or Immunoparesis with reduction of
2 uninvolved immunoglobulin isotypes and/or *Serum involved:uninvolved FLC
ratio >=8 and <100 and/or *Clonal BMPCs >50% to <60%
# Laboratory values as defined by the protocol
# Use of highly effective contraceptive methods
Exclusion criteria
# Active multiple myeloma, requiring treatment as defined by the study protocol
# Primary systemic AL (immunoglobulin light chain) amyloidosis
# Prior or concurrent exposure to any of the following: *Approved or
investigational treatments for SMM or multiple myeloma, *Daratumumab or other
anti-CD38 therapies, *Corticosteroids with a dose exceeding 10 mg prednisone
per day or equivalent, *Investigational drug (including investigational
vaccines) or invasive investigational medical device within 4 weeks or 5
half-lives before Cycle 1 Day 1
# Received treatment for a malignancy (other than SMM) within 3 years before
the date of randomization (exceptions in the protocol)
# Known or suspected Chronic Obstructive Pulmonary Disease (COPD) and/or
moderate or severe persistent asthma within the past 2 years
# Known to be seropositive for HIV
#Seropositive for Hepatitis B. Amendment 3 change: Local testing and results
of hepatitis B serology (Includes HBsAg, anti-HBs, and anti-HBc) is required
for all patients prior to randomization when this amendment 3 is implemented.
# Known to be seropositive for hepatitis C
# Concurrent medical or psychiatric condition or disease that is likely to
interfere with the study procedures or results, or that in the opinion of the
investigator would constitute a hazard for participating in this study
# Clinically significant cardiac disease
# Pregnant, breast-feeding, or planning to become pregnant while receiving
study treatment or within 3 months after the last dose of daratumumab
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-507143-11-00 |
| EudraCT | EUCTR2016-001205-16-NL |
| ClinicalTrials.gov | NCT03301220 |
| CCMO | NL62824.056.17 |