The primary objective is to compare the efficacy of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival (PFS) in subjects with newly diagnosed…
ID
Source
Brief title
Condition
- Haematological disorders NEC
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is PFS, which is defined as the duration from the date of
randomization to either progressive disease, or death, whichever occurs first.
Disease progression will be determined according to the IMWG criteria.
Secondary outcome
Time to disease progression (TTP) is defined as the time from the date of
randomization to the date of first documented evidence of PD, as defined in the
IMWG criteria. For subjects who have not progressed, data will be censored at
the date of the disease evaluation before the start of any subsequent
anti-myeloma therapy.
*
CR rate, defined as the percentage of subjects achieving CR, as defined:
* -Negative immunofixation of serum and urine, and
* -Disappearance of any soft tissue plasmacytomas, and
* -<5% plasma cells (PCs) in bone marrow
* -For those subjects with negative serum M-protein quantitation by
electrophoresis (SPEP) and suspected daratumumab interference on
immunofixation, a reflex assay using anti-idiotype antibody will be utilized to
confirm daratumumab interference and rule out false positive immunofixation.
Patients who have confirmed daratumumab interference, but meet all other
clinical criteria for CR or sCR, will be considered CR/sCR.
MRD negativity rate, defined as the proportion of subjects assessed as MRD
negative, at any timepoint
after the date of randomization.
Progression-free Survival on Next line of Therapy (PFS2), defined as the time
from randomization to progression on the next line of treatment or death,
whichever comes first. Disease progression will be based on investigator
judgment. For those subjects who are still alive and not yet progressed on the
next line of treatment, they will be censored on the last date of follow-up.
Overall survival (OS), measured from the date of randomization to the date of
the
subject*s death. If the subject is alive or the vital status is unknown, then
the subject*s data will be
censored at the date the subject was last known to be alive.
*
Time to next treatment, defined as the time from randomization to the start of
the next-line treatment.
sCR rate, defined as the percentage of subjects achieving CR in addition to
having a normal free light
chain (FLC) ratio and an absence of clonal cells in bone marrow by
immunohistochemistry,
immunofluorescence, 2-4 color flow cytometry
*
Overall response rate (ORR), defined as the proportion of subjects who achieve
CR or PR, according to the IMWG criteria, during or after the study treatment.
*
Proportion of subjects who achieve VGPR or better, defined as the proportion of
subjects achieving VGPR and CR (including sCR) according to the IMWG criteria
during or after the study treatment at the time of data cutoff.
Time to response, defined as the time between the randomization and the first
efficacy evaluation that
the subject has met all criteria for PR or better. For subjects without
response, data will be censored
either at the date of progressive disease or, in the absence of progressive
disease, at the last disease
evaluation before the start of subsequent anti-myeloma therapy.
*
Duration of response, calculated from the date of initial documentation of a
response (CR or PR) to the date of first documented evidence of progressive
disease, as defined in the IMWG criteria. For subjects who have not progressed,
data will be censored at the last disease evaluation before the start of any
subsequent anti-myeloma therapy.
To evaluate clinical efficacy of DRd in high risk molecular subgroups compared
to Rd alone.
*
To evaluate the impact of DRd compared to Rd on patient-reported perception of
global health.
Background summary
Multiple myeloma is a heterogeneous disease, with a course that varies on the
basis of both disease- and host-related factors (eg, age, renal function,
stage, chromosomal abnormalities). Multiple myeloma causes significant
morbidity and mortality.
For those not considered suitable for high-dose chemotherapy and ASCT,
longer-term treatment with multi-agent combinations including alkylators,
high-dose steroids, and novel agents are currently considered as standards of
care.
Study objective
The primary objective is to compare the efficacy of daratumumab when combined
with lenalidomide and dexamethasone (DRd) to that of lenalidomide and
dexamethasone (Rd), in terms of progression-free survival (PFS) in subjects
with newly diagnosed myeloma who are not candidates for high dose chemotherapy
and autologous stem cell transplant
Study design
This is a randomized, open-label, active controlled, parallel-group,
multicenter study
Intervention
Daratumumab (16 mg/kg) will be administered by IV infusion to subjects in Arm B
initially once every week for 8 weeks; then once every other week for 16 weeks;
thereafter once every 4 weeks until documented progression, unacceptable
toxicity, or study end.
Lenalidomide will be self-administered at a dose of 25 mg PO each day on Days 1
through 21 of each 28 day cycle.
Dexamethasone (or equivalent in accordance with local standards) will be
administered at a total dose of 40 mg weekly.
Study burden and risks
The primary hypothesis of this study is that daratumumab in combination with Rd
will prolong PFS as compared with Rd alone in subjects with newly diagnosed
multiple myeloma who are ineligible for high dose chemotherapy and autologous
stem cell transplant.
Turnhoutseweg 30
Beerse 2340
BE
Turnhoutseweg 30
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
Participant must have documented multiple myeloma and measurable disease
defined as: 1) monoclonal plasma cells in the bone marrow greater than or equal
to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma; 2)
measurable disease as defined by any of the following: (a) immunoglobulin (Ig)
G myeloma (serum monoclonal paraprotein [M-protein] level >=1.0
gram/deciliter [g/dL] or urine M-protein level >=200 milligram[mg]/24
hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein
level >=0.5 g/dL or urine M-protein level >=200 mg/24 hrs); or (c) light
chain multiple myeloma (serum immunoglobulin free light chain >=10 mg/dL and
abnormal serum immunoglobulin kappa lambda free light chain ratio), -
Participant must have an Eastern Cooperative Oncology Group (ECOG) performance
status score of 0, 1, or 2 - Participants who are newly diagnosed and not
considered for high-dose chemotherapy due to: being age >=65 years; or
participants less than (<) 65 years with presence of important comorbid
condition(s) likely to have a negative impact on tolerability of high dose
chemotherapy with stem cell transplantation. Sponsor review and approval of
participants below 65 years of age is required before randomization, - Women of
childbearing potential must commit to either abstain continuously from sexual
intercourse or to use 2 methods of reliable birth control simultaneously as
deemed appropriate by the Investigator. Contraception must begin 4 weeks prior
to dosing, - Man, who is sexually active with a woman of child-bearing
potential and has not had a vasectomy, must agree to use an adequate
contraception method as deemed appropriate by the Investigator, and must also
agree to not donate sperm during the study and for 4 weeks after last dose of
lenalidomide and 4 months after last dose of daratumumab
Exclusion criteria
Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of
undetermined significance (presence of serum M-protein <3 g/dL; absence of
lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to
the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma
with absence of related organ or tissue impairment end organ damage), -
Participant has a diagnosis of Waldenström*s disease, or other conditions in
which IgM M protein is present in the absence of a clonal plasma cell
infiltration with lytic bone lesions, - Participant has a history of malignancy
(other than multiple myeloma) within 5 years before the date of randomization
(exceptions are squamous and basal cell carcinomas of the skin and carcinoma in
situ of the cervix, or malignancy that is considered cured with minimal risk of
recurrence within 5 years), - Participant has prior or current systemic therapy
or SCT for multiple myeloma, with the exception of an emergency use of a short
course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of
corticosteroids before treatment, - Participant has had radiation therapy
within 14 days of randomization, - Participant has known chronic obstructive
pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second
[FEV1] <60% of predicted normal), persistent asthma, or a history of asthma
within the last 2 years (intermittent asthma is allowed).
Participants with known or suspected COPD or asthma must have a FEV1 test
during Screening
- Participant is known to be seropositive for history of human immunodeficiency
virus (HIV) or known to have active hepatitis B or hepatitis C
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 |
|---|---|
| EudraCT | EUCTR2014-002273-11-NL |
| ClinicalTrials.gov | NCT02252172 |
| CCMO | NL52584.028.15 |