Multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each potential subject must satisfy all of the following criteria to be enrolled in the study: 1.At least 18 years of age 2.documented with multiple myeloma as defined by the criteria below: a)Multiple myeloma diagnosis according to the IMWG diagnostic criteria b)Measurable disease at Screening as defined by any of the following: i) Serum M-protein level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or ii) Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin FLC =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. 3. Evidence of a response (partial response [PR] or better based on investigator's determination of response by IMWG criteria) to at least 1 prior treatment regimen. 4. Relapsed or refractory disease as defined below: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed PD by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (= 1.0 × 10^9/Litre (L) c) Platelet count >= 50 × 10^9/L (transfusions are not permitted within 7 days of testing to achieve this minimum platelet count) d) Aspartate aminotransferase (AST) 20 milliletre per minute (mL/min) per 1.73m^2 h) Albumin-corrected serum calcium <=14 mg/dL (<= 3.5 mmol/L) or free ionized calcium <= 6.5 mg/dL (<=1.6 mmol/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, hormonal [birth control pills, injections, hormonal patches, vaginal rings or im
Exclusion criteria
Exclusion criteria: Any potential subject who meets any of the following criteria will be excluded from participating in the study: 1.Received daratumumab or other anti-CD38 therapies previously 2.Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, 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)before treatment.A list of anti myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (SIPPM). 3.Received autologous stem cell transplant within 12weeks before the date of randomization,or the subject has previously received allogeneic stem cell transplant (regardless of timing) 4.Plans to undergo a stem cell transplant prior to progression of disease on this study 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.Clinical signs of meningeal involvement of multiple myeloma 7.Either of the following: a)Known chronic obstructive pulmonary disease(COPD)with a forced expiratory volume in 1 second (FEV1) is 470 msec. 11.Known allergies,hypersensitivity,or intolerance to any of the study drugs,hyaluronidase,mAbs,human proteins, or their excipients, or known sensitivity to mammalian-derived products. 12.Plasma cell leukemia (>2.0 × 109/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is : ? To show that subcutaneous (SC) administration of daratumumab coformulated with recombinant human hyaluronidase PH20 (Dara-SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara- IV) in terms of the overall response rate (ORR) ? To show that Dara-SC is non-inferior to Dara-IV in terms of the maximum trough concentration (Ctrough);Secondary Objective: ? To assess the pharmacokinetics and immunogenicity of Dara-SC and Dara-IV ? To evaluate the safety of Dara-SC and Dara-IV ? To evaluate the clinical benefit of Dara-SC and Dara-IV ? To evaluate the immunogenicity of recombinant human hyaluronidase (rHuPH20) following Dara- SC administration ? To evaluate patient-reported satisfaction with Dara-SC and Dara-IV;Primary end point(s): The co-primary endpoints of this study are: ? ORR, defined as the proportion of subjects with a PR or better according to the International Myeloma Working Group (IMWG) response criteria ? Maximum Ctrough, defined as the serum predose concentration of daratumumab on Cycle 3 Day 1 ;Timepoint(s) of evaluation of this end point: 1. 6 months after 480 subjects have been randomized. 2. Cycle 3 Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Rate of infusion-related reaction (IRRs) 2. PFS, defined as the time from randomization to the date of disease progression or death dueto any cause, whichever occurs first 3. Rate of VGPR or better, according to the IMWG response criteria 4. Rate of CR or better, according to the IMWG response criteria 5. Time to next therapy (TNT), defined as the time from randomization to the start of the first subsequent anti-cancer therapy 6. Overall survival (OS), defined as the time from randomization to the date of death 7. Patient-reported satisfaction with therapy, defined as the mean of responses to 7 of 9 questions in the modified Cancer Therapy Satisfaction Questionnaire (modified-CTSQ) 8. Duration of response, defined as date of onset of first response until date of disease progression or death 9. Time to response, defined as the time from randomization until onset of first response;Timepoint(s) of evaluation of this end point: There is no interim analysis planned for the primary or secondary endpoints. Both sets of endpoints will be analyzed 6 months after the last subject has been randomized. | — |
Countries
Australia, Brazil, Canada, China, Czech Republic, France, Greece, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry group
Janssen-Cilag International N.V.
Outcome results
None listed