A Clinical Study of Daratumumab Subcutaneous (Dara-SC) Administrationin Combination with Carfilzomib and Dexamethasone (DKd) Compared withCarfilzomib and Dexamethasone (Kd) in Participants with Multiple Myelomawho have been Previously Treated with Daratumumab to EvaluateDaratumumab 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-DE
- 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.
2.1 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.
3.1 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.
4.1. 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.
5.1 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 (Appendix 7).
7. Pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:
a) hemoglobin =8g/dL (=5 mmol/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 7 in Protocol Am on pg.40.
8.2. 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 contraceptives or a hormonal method of contraception that is associated with a risk of thro
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Criterion deleted per Amendment 2/DEU-1
2. Previoustreatment with carfilzomib
3. Previous treatment with daratumumab within the last 3 months prior to randomization
4.1 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
8.1 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 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 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
12.1 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
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 myeloma
17. Please see the complete list of criteria 17 on pg43 of the Protocol Am
18.1 Participant is:
a) Known to be seropositive for human immunodeficiency virus (HIV), with 1 or more of the following:
i. Not receiving highly active a
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