Multiple Myeloma plasma cell myeloma
Conditions
Interventions
Participants will be treated with Kd alone (Arm A) or Dara SC in combination
with Kd (Arm B) in 28 day cycles.
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 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 =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 =50×10^9/L. Transfusions are not permitted within 7 days of testing to achieve this minimum platelet count. d) aspartate aminotransferase (AST) =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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objectives The primary objective is to compare the efficacy (rate of very good partial response [VGPR] or better as best response as defined by the International Myeloma Working Group [IMWG] criteria) of Dara SC in combination with Kd with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment. Primary Endpoint The primary endpoint of this study is the rate of VGPR or better as defined by the IMWG criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objectives The secondary objectives are: To further characterize the efficacy (progression-free survival [PFS], overall survival [OS], overall response rate [ORR], rate of complete response [CR]/stringent complete response [sCR]) of Dara SC in combination with Kd To evaluate the minimal residual disease (MRD) negativity rate and durability of MRD negativity status To characterize the safety of Dara SC in combination with Kd To determine time to next treatment To evaluate the pharmacokinetics (PK) of Dara SC To determine the immunogenicity of daratumumab and recombinant human hyaluronidase PH20 (rHuPH20) Secondary Endpoints The secondary endpoints are: ORR (rate of partial response [PR], VGPR, CR, sCR) Rate of CR/sCR PFS OS MRD negativity rate Time to next treatment Serum daratumumab concentrations Prevalence and incidence of anti-daratumumab antibodies and anti-rHuPH20 antibodies | — |
Countries
Netherlands
Outcome results
None listed