A Clinical 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 Intravenous (Dara-IV) to Evaluate Daratumumab Retreatment
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004185-34-GR
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 230
1. At least 18 years of age.
2. Documented multiple myeloma as defined by the criteria below:
Multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria. 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 IV therapy with response duration of at least 4 months.
4.1. Participants must have progressed from or be refractory to their last line of treatment. 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 or 2 prior line(s) of treatment of which one contained Dara-IV, and completed Dara-IV 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.Please see the complete list of criteria in 7 in Protocol Am on pg.39.
8.1. 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, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). A reduction in the effectiveness of oral contraceptives during carfilzomib treatment cannot be excluded. In addition, because of the increased risk of venous thromboembolic events associated with carfilzomib, women should avoid the use of hormonal contraceptives that are associated with a risk of thrombosis during treatment with carfilzomib. Women of childbearing potential who are using oral con
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Previous treatment with Dara-SC.
2. Previoustreatment with carfilzomib.
3. Previous treatment with daratumumab within the last 3 months prior to randomization.
4. Discontinuation of Dara-IV 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.
8.1 Received an investigational int7. 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 bervention (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 5 PK half-lives of
the treatment from the date of randomization, whichever is longer)
9.Pregnant, or breast-feeding, or planning to become pregnant whileenrolled 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.
12.1. Received anti-myeloma treatment within 2 weeks or 5 PK half-lives
of the treatment from the date of randomization, whichever is longer.
The only exception is emergency use of a short course of corticosteroids
(equivalent of dexamethasone 40 mg/day for a maximum of 4 days; see
Appendix 10) 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.
For full exclusion criteria including 13-18, refer page no: 40 to 44 of the protocol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method