A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Drug: Dara SCDrug: Dara IV
- Registration Number
- NCT03277105
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated 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) and maximum trough concentration (Ctrough).
- Detailed Description
The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of the data collection period, approximately 24 months after the last participant was randomized or when the median overall survival for both arms has been reached, whichever occurs first. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 522
-
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:
-
Multiple myeloma diagnosis according to the IMWG diagnostic criteria
-
Measurable disease at Screening as defined by any of the following:
- Serum M-protein level >=1.0 gram per deciliter (g/dL) 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
-
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dara SC Dara SC Participants will receive a fixed dose of daratumumab as 1800 milligram (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 thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. Dara IV Dara SC Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. 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. Dara IV Dara IV Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. 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.
- Primary Outcome Measures
Name Time Method Maximum Trough Concentration (Ctrough) of Daratumumab Predose on Cycle 3 Day 1 (each cycle of 28 days) Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Overall Response Rate (ORR) Up to 1 year 8 months ORR was defined as the percentage of participants who achieved 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 less than (\<) 200 milligrams (mg)/24 hours, If the serum and urine M-proteins are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels were required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-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 was also required.
- Secondary Outcome Measures
Name Time Method Time to Next Therapy Up to 3 years Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
Progression Free Survival (PFS) Up to 3 years PFS was defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. IMWG criteria for PD: 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 \>=200 mg/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.
Percentage of Participants With Complete Response (Including sCR) or Better Up to 3 years CR or better was defined as percentage of participants with a CR or better (CR or stringent complete response \[sCR\]) based on computerized algorithm as per IMWG criteria. 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.
Overall Survival (OS) Up to 3 years OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR) Up to 3 years Percentage of participants with treatment-emergent infusion-related reactions were reported.
Time to Very Good Partial Response (VGPR) or Better Up to 3 years Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better.
Percentage of Participants With Very Good Partial Response (VGPR) or Better Up to 3 years VGPR or better was defined as the percentage of participants who achieved VGPR or better (VGPR, complete response (CR) or stringent complete response \[sCR\]), based on computerized algorithm as per 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 \>=90 percent (%) reduction in serum M-protein plus urine M-protein \<100 milligrams (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 FLC ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.
Duration of Response Up to 3 years Duration of response was defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria. PD was defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be \>= 0.5 g/dL and \>=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be \> 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time to Partial Response (PR) or Better Up to 3 years Time to PR or better was defined as the time from randomization until onset of first response of PR or better.
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 1 (Days 8,15 and 22), Cycle 2 (Days 1,8,15 and 22), Cycle 3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 and 22 (Day 1) Modified-CTSQ contain 9 items (2 items for Thoughts about Cancer Therapy and 7 items in a defined domain of Satisfaction with Therapy) specific to satisfaction with therapy and for comparison of SC and IV administration. Satisfaction with therapy was calculated based on 7-items using 5-point verbal rating scale, where 1= never and 5= always. Scores were averaged and transformed to a 0-100 scale; higher scores represent better health. At least 5 of the 7 items within the Satisfaction with Therapy domain had to be completed to calculate a domain score. No domain score was calculated for Thoughts about Cancer Therapy.
Time to Complete Response (CR) or Better Up to 3 years Time to CR or better was defined as the time from randomization until onset of first CR or better.
Trial Locations
- Locations (146)
Azienda USL di Piacenza
🇮🇹Piacenza, Italy
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
St. Vincent's Hospital Melbourne
🇦🇺Fitzroy, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
Hospital Das Clinicas Da Faculdade De Medicina Da USP
🇧🇷São Paulo, Brazil
Calvary Mater Newcastle Hospital
🇦🇺Waratah, Australia
Fundacao Pio XII
🇧🇷Barretos, Brazil
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Fakultnà nemocnice Olomouc
🇨🇿Olomouc, Czechia
Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
🇨🇿Praha 2, Czechia
Royal Marsden Hospital
🇬🇧Surrey, United Kingdom
Ospedale Villa Sofia-Cervello
🇮🇹Palermo, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
CHU Caen - Côte de Nacre
🇫🇷Caen, France
Hillel Yaffe Medical Center - Oncology
🇮🇱Hadera, Israel
Rambam Med.Center - Hematology Institute
🇮🇱Haifa, Israel
Chugoku Central Hospital
🇯🇵Fukuyama, Japan
CHU Poitiers - Hôpital la Milétrie
🇫🇷Poitiers, France
Università di Roma La Sapienza
🇮🇹Roma, Italy
Sheba Medical Center Tel Hashomer
🇮🇱Ramat Gan, Israel
Policlinico Sant'Orsola Malpighi
🇮🇹Bologna, Italy
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
A.O.U. Città della Salute e della Scienza
🇮🇹Torino, Italy
Ogaki Municipal Hospital
🇯🇵Gifu, Japan
Fukuoka University Hospital
🇯🇵Fukuoka, Japan
Iwate Medical University Hospital
🇯🇵Iwate, Japan
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱Lublin, Poland
Hosp. Quiron Madrid Pozuelo
🇪🇸Pozuelo de Alarcon, Spain
State Institution 'National Scientific Center for Radiation Medicine of NAMS of Ukraine'
🇺🇦Kiev, Ukraine
Falu Lasarett
🇸🇪Falun, Sweden
Hosp. Univ. Dr. Peset
🇪🇸Valencia, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Helsingborgs lasarett
🇸🇪Helsingborg, Sweden
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
CHU de Boreaux
🇫🇷Pessac, France
Centre hospitalier Lyon-Sud
🇫🇷Pierre-Bénite, France
CHU Nancy Brabois
🇫🇷Vandoeuvre Les Nancy, France
Kobe City Medical Center General Hospital
🇯🇵Hyogo, Japan
Matsuyama Red Cross Hospital
🇯🇵Matsuyama, Japan
Japanese Red Cross Nagoya Daini Hospital
🇯🇵Nagoya, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Japan
Hospital das Clinicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
🇧🇷Florianopolis, Brazil
Instituto de Educacao, Pesquisa e Gestao em Saude
🇧🇷Rio de Janeiro, Brazil
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Victoria Hospital
🇨🇦London, Ontario, Canada
QEII Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
CHU de Québec -L'Hôtel-Dieu de Québec
🇨🇦Québec, Quebec, Canada
Penza Regional Oncology Dispensary
🇷🇺Penza, Russian Federation
National Cancer Center
🇰🇷Goyang-Si, Korea, Republic of
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Alfred Health
🇦🇺Melbourne, Australia
Fundacao Doutor Amaral Carvalho
🇧🇷Jau, Brazil
The Queen Elizabeth Hospital
🇦🇺Woodville South, Australia
Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo
🇧🇷Passo Fundo, Brazil
Instituto Joinvilense de Hematologia e Oncologia Ltda-Centro de Hematologia e Oncologia
🇧🇷Joinville, Brazil
CEHON
🇧🇷Salvador, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base
🇧🇷Sao Jose do Rio Preto, Brazil
Clinica Sao Germano
🇧🇷São Paulo, Brazil
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
The Gordon & Leslie Diamond Health Care Center
🇨🇦Vancouver, British Columbia, Canada
Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
🇨🇿Plzen, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Alexandra General Hospital of Athens
🇬🇷Athens Attica, Greece
CHU de Nantes hotel Dieu
🇫🇷Nantes Cedex 1, France
Hopital Claude Huriez
🇫🇷Lille Cedex, France
Carmel Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Rabin Medical Center Beilinson Campus
🇮🇱Petah Tikva, Israel
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Gunma University Hospital
🇯🇵Gunma, Japan
University Hospital Kyoto Perfectural University of Medicine
🇯🇵Kyoto, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
National Hospital Organization Sendai Medical Center
🇯🇵Sendai-City, Japan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Japanese Red Cross Medical Center
🇯🇵Shibuya, Japan
National Hospital Organization Shibukawa Medical Center
🇯🇵Shibukawa, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
🇵🇱Brzozow, Poland
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
The Catholic University of Korea Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Szpitale Pomorskie Sp z o o
🇵🇱Gdynia, Poland
Wojewodzki Szpital Specjalistyczny w Legnicy
🇵🇱Legnica, Poland
S.P. Botkin Moscow City Clinical Hospital
🇷🇺Moscow, Russian Federation
Emergency Hospital of Dzerzhinsk
🇷🇺Dzerzhinsk, Russian Federation
City Clinical Hospital # 40
🇷🇺Moscow, Russian Federation
Nizhniy Novgorod Region Clinical Hospital
🇷🇺Nizny Novgorod, Russian Federation
Ryazan Regional Clinical Hospital
🇷🇺Ryazan, Russian Federation
Saint Petersburg City Hospital #15
🇷🇺Saint-Petersburg, Russian Federation
Samara Region Clinical Hospital
🇷🇺Samara, Russian Federation
Mykolaiv Regional Clinical Hospital
🇺🇦Mykolaiv, Ukraine
Ekaterinburg City Clinical Hospital # 7
🇷🇺Ekaterinburg, Russian Federation
Clinical Research Institute of Hematology and Transfusiology
🇷🇺St-Petersburg, Russian Federation
Hosp. Univ. Germans Trias I Pujol
🇪🇸Badalona, Spain
Oncology Dispensary of Komi Republic
🇷🇺Syktyvkar, Russian Federation
Hosp. Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. Dr. Josep Trueta
🇪🇸Girona, Spain
Hosp. Univ. Virgen de Las Nieves
🇪🇸Granada, Spain
Hosp. de Leon
🇪🇸Leon, Spain
Hosp. Univ. de Canarias
🇪🇸La Laguna, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. Infanta Leonor
🇪🇸Madrid, Spain
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp. Clinico Univ. de Salamanca
🇪🇸Salamanca, Spain
Karolinska University Hospital, Huddinge
🇸🇪Huddinge, Sweden
Skanes universitetssjukhus
🇸🇪Lund, Sweden
Norrlands University Hospital
🇸🇪Umea, Sweden
China Medical University Hospital
🇨🇳Taichung City, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung,, Taiwan
SI Grigoriev Institute for Medical Radiology National Academy of Medical Science of Ukraine
🇺🇦Kharkiv, Ukraine
Communal Nonprofit Enterprise 'Cherkasy Regional Oncology Dispensary Of Cherkasy Regional Council'
🇺🇦Cherkasy, Ukraine
Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center
🇺🇦Dnepropetrovsk, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦Ivano-Frankivsk, Ukraine
Kiev Marrow Transplantation Center, Bone Marrow Transplantation Department
🇺🇦Kiev, Ukraine
National Cancer Institute, Dept. of chemotherapy of hemoblastosis
🇺🇦Kiev, Ukraine
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Leicester Royal Infirmary - Haematology
🇬🇧Leicester, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Ukrainian Medical Stomatological Academy, Poltava Regional Clinical Hospital
🇺🇦Poltava, Ukraine
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Guys St Thomas Hospital
🇬🇧London, United Kingdom
Christie Hospital NHS Trust
🇬🇧Manchester, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
🇵🇱Chorzów, Poland
Chang-Hua Christian Hospital
🇨🇳Changhua, Taiwan
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
🇵🇱Poznan, Poland
Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
🇵🇱Warszawa, Poland
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Institute of Blood Pathology and Transfusion Medicine of AMS of Ukraine
🇺🇦Lviv, Ukraine
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada