A Phase 2 Study of Daratumumab Subcutaneous (Dara-SC) Administration in Combination with Carfilzomib and Dexamethasone (DKd) Compared with Carfilzomib and Dexamethasone (Kd) in Participants with Multiple Myeloma who have been Previously Treated with Daratumumab to Evaluate Daratumumab Retreatment
- Conditions
- Multiple Myelomaplasma cell myeloma10047954
- Registration Number
- NL-OMON55384
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
Each potential participant must satisfy all of the following criteria to be
enrolled in the study:
1. At least 18 years of age.
2. Documented multiple myeloma as defined by the criteria below: Measurable
disease at screening as defined by any of the following: Serum M-protein level
>=1.0 g/dL in participants with immunoglobulin G (IgG) type, or serum M-protein
level >=0.5 g/dL in participants with non- IgG type, or urine M-protein level
>=200 mg/24 hours; or Light chain multiple myeloma without measurable disease in
the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL
and abnormal serum immunoglobulin kappa lambda FLC ratio.
3. Evidence of a response (partial response or better based on investigator*s
determination of response by IMWG criteria) to daratumumab-containing therapy
with response duration of at least 4 months.
4. Relapsed or refractory disease as defined below: Relapsed disease is defined
as an initial response to previous treatment, followed by confirmed PD by IMWG
criteria >60 days after cessation of treatment. Refractory disease is defined
as <25% reduction in M-protein or confirmed PD by IMWG criteria during previous
treatment or <=60 days after cessation of treatment.
5. Received 1 to 3 prior line(s) of treatment of which one contained
Daratumumab and completed Daratumumab at least 3 months prior to randomization.
A single line of therapy may consist of 1 or more agents, and may include
induction, hematopoietic stem cell transplantation, and maintenance therapy.
Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no
more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be
considered prior lines of therapy.
6. ECOG Performance Status score of 0, 1, or 2.
7. Pretreatment clinical laboratory values meeting the following criteria
during the Screening Phase:
a) hemoglobin >=8 g/dL (>=5mmol/L) (without prior RBC transfusion within 7 days
before the laboratory test; recombinant human erythropoietin use is permitted);
b) absolute neutrophil count (ANC) >=1.0 × 10^9/L (prior growth factor support
is permitted but must be without support within the 7 days prior to the
laboratory test);
c) platelet count >=75 ×10^9/L for participants in whom <50% of bone marrow
nucleated cells are plasma cells; otherwise platelet count of >=50×10^9/L.
Transfusions are not permitted within 7 days of testing to achieve this minimum
platelet count.
d) aspartate aminotransferase (AST) <=2.5 × upper limit of normal (ULN);
e) alanine aminotransferase (ALT) <=2.5 × ULN;
f) total bilirubin <=1.5 × ULN; except in participants with congenital
bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=1.5×
ULN is required);
g) estimated creatinine clearance (CrCl) >=20mL/min per 1.73m^2. CrCl to be
calculated using estimated glomerular filtration rate Modification of Diet in
Renal Disease (MDRD) formula.
h) albumin-corrected serum calcium <=14 mg/dL (<=3.5 mmol/L) or free ionized
calcium <=6.5 mg/dL (<=1.6mmol/L)
8. Women of childbearing potential must commit to either abstain continuously
from heterosexual sexual intercourse or to use 2 methods of reliable birth
control simultaneously. This includes one highly effective form of
contraception (tubal ligation, intrauterine device, hormon
Any potential participant who meets any of the following criteria will be
excluded from participating in the study:
2. Previous treatment with carfilzomib.
3. Previous treatment with daratumumab within the last 3 months prior to
randomization.
4. Discontinuation of Daratumumab due to a daratumumab-related AE.
5. History of malignancy (other than multiple myeloma) unless all treatment of
that malignancy was completed at least 2 years before consent and the patient
has no evidence of disease. Further exceptions are squamous and basal cell
carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other
non-invasive lesion, that in the opinion of the investigator, with concurrence
with the sponsor's medical monitor, is considered cured with minimal risk of
recurrence within 3 years.
6. Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase,
mAbs, human proteins, or their excipients (refer to the IB), or known
sensitivity to mammalian derived products. Known history of allergy to Captisol
(a cyclodextrin derivative used to solubilize carfilzomib).
7. Contraindications to the use of any components of the backbone treatment
regimens, per local prescribing information.
8. Received an investigational intervention (including investigational
vaccines) or used an invasive investigational medical device within 4 weeks
before randomization (except for investigational anti-myeloma treatments, which
cannot be taken within 2 weeks or 5PK half-lives of the treatment from the
first dose of daratumumab, whichever is longer, before the date of
randomization).
9. Pregnant, or breast-feeding, or planning to become pregnant while enrolled
in this study or within 3 months after the last dose of study intervention.
10. Plans to father a child while enrolled in this study or within 3 months
after the last dose of study intervention.
11. Any condition for which, in the opinion of the investigator, participation
would not be in the best interest of the participant (eg, compromise the
well-being) or that could prevent, limit, or confound the protocol-specified
assessments.
12. Received anti-myeloma treatment within 2 weeks or 5 PK half-lives of the
treatment from the first dose of daratumumab, whichever is longer, before the
date of randomization. The only exception is emergency use of a short course of
corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days)
up to 21 days before treatment. A list of anti-myeloma treatments with the
corresponding PK half-lives is provided in the Site Investigational Product
Procedures Manual.
13. Received autologous stem cell transplant within 12 weeks before the date of
randomization, or the participant has previously received allogeneic stem cell
transplant (regardless of timing).
14. Plans to undergo a stem cell transplant prior to progression of disease on
this study.
15. Focal radiation therapy within 14 days prior to randomization with the
exception of palliative radiotherapy for symptomatic management but not on
measurable extramedullary plasmacytoma. Radiotherapy within 14 days prior to
randomization on measurable extramedullary plasmacytoma is not permitted even
in the setting of palliation for symptomatic management.
16. Clinical signs of meningeal involvement of multiple myel
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary objectives<br /><br><br /><br>The primary objective is to compare the efficacy (rate of very good partial<br /><br>response [VGPR] or better as best response as defined by the International<br /><br>Myeloma Working Group [IMWG] criteria) of Dara SC in combination with Kd with<br /><br>the efficacy of Kd in participants with relapsed refractory multiple myeloma<br /><br>who were previously exposed to daratumumab to evaluate daratumumab retreatment.<br /><br><br /><br>Primary Endpoint<br /><br><br /><br>The primary endpoint of this study is the rate of VGPR or better as defined by<br /><br>the IMWG criteria.</p><br>
- Secondary Outcome Measures
Name Time Method