A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma
Fujikawa Ei
Janssen Pharmaceutical K.K.
5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
Janssen Pharmaceutical K.K.
5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
completed
April. 11, 2018
480
Interventional
Randomized
No Masking
treatment purpose
3
- Evidence of a response (Partial response [PR] or better based on investigator's determination of response by international myeloma working group [IMWG] criteria) to at least 1 prior treatment regimen
- Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). 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 milligram/day [mg/day] for 4 days) would not be considered prior lines of therapy
- Documented multiple myeloma as defined by the criteria below:
1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
2. Measurable disease at Screening as defined by any of the following:
a) Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
b) 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
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Meet the clinical laboratory criteria as specified in the protocol
- Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization
- Received daratumumab or other anti-CD38 therapies previously
- 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
- 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)
- Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)
- 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.
20age old over
No limit
Both
Multiple Myeloma
investigational material(s)
Generic name etc : Dara SC
INN of investigational material : daratumumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Participants will receive a fixed dose of daratumumab as 1800milligram (mg) subcutaneously (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and there after until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.
control material(s)
Generic name etc : Dara IV (JNJ-54767414)
INN of investigational material : daratumumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Participants will receive daratumumab for intravenous infusion(Dara IV) 16 mg/kg by once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks at Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
For Participants still receiving treatment with Dara-IV at the time of Protocol Amendment 4 the duration of infusion may be shortened to a 90-minute infusion or participants will have the option to switch to Dara 1800 mg subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.
efficacy
Overall Response Rate (ORR)
At 6 months after 480 participants have been randomized (approximately 2years)
The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to lesss than (<) 200 mg/24hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the Mprotein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place ofM+H30-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
pharmacokinetics
Maximum Trough Concentration (Ctrough) of Daratumumab
Cycle 3 (each cycle 28 days) Day 1
Maximum Ctrough is defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
safety
Percentage of participants With Infusion-Related Reactions (IRR)
At 6 months after 480 participants have been randomized (approximately 2years)
The Percentage of Participants with infusion reactions will be reported.
efficacy
Progression-Free Survival (PFS)
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized(approximately 3 years)
PFS is defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. According to IMWG criteria: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200mg/24 hours), Participants without measurable serum and urine
Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%),
definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
efficacy
Very Good Partial Response (VGPR) or Better Rate
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years)
The VGPR or better rate, defined as the proportion of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]) according IMWG
criteria during or after the study treatment.
IMWG criteria for VGPR:Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram(mg)/24 hours, CR: Negative immunofixation on the serum and
urine, disappearance of any soft tissue plasmacytomas and <5%plasma cellS (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), munofluorescencea or 2- to 4 color flow cytometry
efficacy
Complete Response (Including sCR) or Better Rate
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years)
Complete response is based on serum M-Protein assessments.IMWG criteria for CR: Negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by IHC, immunofluorescencea or 2- to 4 color flow cytometry.
efficacy
Time to Next Treatment
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized(approximately 3 years)
Time to next therapy is defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
efficacy
Overall Survival (OS)
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years)
OS is defined as the time from the date of randomization to the date of the participant's death.
efficacy
Patient-Reported Satisfaction With Therapy
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years)
Patient-reported satisfaction with therapy is defined as the mean of responses to 7 of 9 questions in the modified cancer therapy
satisfaction questionnaire (modified-CTSQ). Modified-CTSQ contain 9 items specific to satisfaction with therapy and for comparison of IV
with SC administration. Satisfaction with therapy is calculated based on 7-items using 5-point verbal rating scale, 1, never; 5, always. Scores will be averaged and transformed to a 0-100 scale;
higher scores represent better health.
efficacy
Duration of Response
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years)
Duration of response is defined as date of onset of first response until date of disease progression or death.
efficacy
Time to response
At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years)
Time to response is defined as the time from randomization until onset of first response.
