Primary Objective: • To compare efficacy of once-weekly KRd (56 mg/m2 ) to twice-weekly KRd (27 mg/m2) in subjects with RRMM with 1 to 3 prior lines of therapyKey Secondary Objectives: • To compare progression-free survival (PFS) between treatment…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
bloedcel kanker
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
overall response, defined as the best overall response of stringent complete
response [sCR], complete response [CR], very good partial response [VGPR], and
partial response [PR] per International Myeloma Working Group Uniform Response
Criteria [IMWG-URC]) over the duration of the study
Secondary outcome
- PFS over the duration of the study
- convenience as measured by the Patient-reported Convenience With
Carfilzomib-dosing Schedule Question after cycle 4 of treatment
- incidence of treatment-emergent adverse events
- time to response (TTR)
- duration of response (DOR)
- time to progression (TTP)
- MRD[-]CR , defined as achievement of CR or better by Independent Review
Committee (IRC) per IMWG-URC and achievement of MRD negativity as assessed by
next-generation sequencing method at a 10-5 threshold over the duration of the
study
- MRD[-] status at 12 months, defined as achievement of MRD negativity at 12
months (± 4 weeks) from randomization, as assessed by next-generation
sequencing method at a 10-5 threshold
- physical functioning and role functioning over time as measured by the
Physical Functioning and Role Functioning scales of the European Organization
for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30
(EORTC QLQ-C30) over the duration of the study
- treatment satisfaction as measured by the Satisfaction With Therapy (SWT)
scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ) after cycle 4 of
treatment
Background summary
Multiple myeloma, a clonal neoplastic proliferation of plasma cells, is the
second most common hematologic malignancy and is responsible for approximately
80 000 annual deaths worldwide (1% of all cancer deaths). The estimated
incidence of multiple myeloma worldwide was 114 000 patients, which represents
0.8% of all cancers. The 5-year prevalence of multiple myeloma worldwide was
estimated 229 000 persons (Ferlay et al, 2015). Multiple myeloma is a disease
of older adults, with a median age at diagnosis of 69 years (Noone et al,
2018). As the world*s older population (age > 65 years) continues to grow (from
8.5% [617 million] of the world*s population in 2013 to a projected 17% [1.6
billion] in 2015) (He et al, 2016), the incidence of multiple myeloma is
expected to increase.
Study objective
Primary Objective:
• To compare efficacy of once-weekly KRd (56 mg/m2 ) to twice-weekly KRd (27
mg/m2) in subjects with RRMM with 1 to 3 prior lines of therapy
Key Secondary Objectives:
• To compare progression-free survival (PFS) between treatment arms
• To compare patient-reported convenience with carfilzomib dosing schedule
between treatment arms
Kindly refer to protocol section 4 for more information on Objectives and
additional secondary objectives and endpoints.
Study design
The study will consist of a screening period of up to 28 days, a treatment
duration of up to 12 cycles of 28 days, a 30-day safety follow-up period, and a
long-term follow-up (every 28 +-7 days) period.
Subjects will receive the study drug(s) determined by randomization for a
maximum of 12 cycles. No crossover between the treatment arms is allowed.
Upon discontinuation from the study treatment for any reason, a safety
follow-up visit will be performed approximately 30 (+3) days after the last
dose of all study drug(s). After discontinuation from study treatment, subjects
who do not have confirmed PD are required to continue follow-up every 28 ± 7
days for survival. After end of study, subjects may continue treatment per
local standard of care at the discretion of the investigator.
Subjects will be randomized in a 1:1 ratio to 1 of 2 arms:
Arm 1: KRd using once-weekly carfilzomib 56 mg/m2
Arm 2: KRd using twice-weekly carfilzomib 27 mg/m2
The overall study design is outlined in the study schema in Section 2.1 of the
protocol.
Intervention
n/a
Study burden and risks
See E9 and E9a
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
• Subject has multiple myeloma with documented relapse or progression after
most recent myeloma treatment.
• Subjects must have at least PR to at least 1 line of prior therapy
• Subjects must have received at least 1 but not more than 3 prior lines of
therapy for multiple myeloma (induction therapy followed by stem cell
transplant and consolidation maintenance therapy will be considered as 1 line
of therapy).
• Prior therapy with a PI is allowed if the patient achieved at least a
PR to most recent treatment with a PI, did not relapse within 60 days of
discontinuation of the PI and the PI was not removed due to toxicity. A
history of prior neuropathy is permitted if this was not grade 3, grade 4 or
grade 2 with pain and if not resolved within the 14 days before enrollment, is
less than or equal to grade 2 without pain.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of < 2
Please refer to section 6.1 of the protocol.
Exclusion criteria
• Waldenström macroglobulinemia
• Multiple myeloma of IgM subtype
• Active congestive heart failure (New York Heart Association [NYHA] Class III
to IV), symptomatic ischemia, uncontrolled arrhythmias, ECG abnormalities,
pericardial disease, or myocardial infarction within 4 months prior to
enrollment
• Uncontrolled hypertension
Please refer to section 6.2 of the protocol.
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 | EUCTR2018-000665-36-NL |
| ClinicalTrials.gov | NCT03859427 |
| CCMO | NL68271.029.18 |