A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03277105
Collaborator
(none)
522
Enrollment
147
Locations
2
Arms
74
Anticipated Duration (Months)
3.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Dara SC
  • Drug: Dara IV
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
522 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date :
Oct 27, 2017
Actual Primary Completion Date :
Jun 27, 2019
Anticipated Study Completion Date :
Dec 26, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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.

Drug: Dara SC
Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 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.

Active Comparator: 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.

Drug: Dara SC
Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 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.

Drug: Dara IV
Participants will receive Dara IV 16 mg/kg 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.
Other Names:
  • JNJ-54767414
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [Up to 2 years]

      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 milligram (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.

    2. 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.

    Secondary Outcome Measures

    1. Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR) [Up to 2 years]

      Percentage of participants with treatment-emergent infusion-related reactions were reported.

    2. Progression Free Survival (PFS) [Up to 2 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 grams 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.

    3. Percentage of Participants With Very Good Partial Response (VGPR) or Better [Up to 2 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.

    4. Percentage of Participants With Complete Response (Including sCR) or Better [Up to 2 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.

    5. Time to Next Therapy [Up to 2 years]

      Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.

    6. Overall Survival (OS) [Up to 2 years]

      OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.

    7. 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.

    8. Duration of Response [Up to 2 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.

    9. Time to Partial Response (PR) or Better [Up to 2 years]

      Time to PR or better was defined as the time from randomization until onset of first response of PR or better.

    10. Time to Very Good Partial Response (VGPR) or Better [Up to 2 years]

      Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better.

    11. Time to Complete Response (CR) or Better [Up to 2 years]

      Time to CR or better was defined as the time from randomization until onset of first CR or better.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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:

    3. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or

    4. 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

    Exclusion Criteria:
    • 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Dana-Farber Cancer InstituteBostonMassachusettsUnited States02215-5418
    2Levine Cancer InstituteCharlotteNorth CarolinaUnited States28204
    3Royal Prince Alfred HospitalCamperdownAustralia2050
    4St. Vincent's Hospital MelbourneFitzroyAustralia3065
    5Alfred HealthMelbourneAustralia3004
    6Fiona Stanley HospitalMurdochAustralia6150
    7Sir Charles Gairdner HospitalNedlandsAustralia6009
    8Calvary Mater Newcastle HospitalWaratahAustralia2298
    9The Queen Elizabeth HospitalWoodville SouthAustralia5011
    10Princess Alexandra HospitalWoolloongabbaAustralia4102
    11Hospital Do Cancer De Barretos - Fundacao Pio XiiBarretosBrazil14784-400
    12Centro de Pesquisas Oncológicas - CEPONFlorianópolisBrazil88034-000
    13Hospital Amaral Carvalho - Centro de Ensino e PesquisaJaúBrazil17210-070
    14Instituto Joinvilensse de Hematologia e OncologiaJoinvilleBrazil89201-260
    15Centro de Pesquisa do Instituto do Câncer- Hospital São Vicente de PauloPasso FundoBrazil99010-090
    16Hospital de Clínicas de Porto AlegrePorto AlegreBrazil90035-903
    17Instituto COI de Pesquisa, Educacao e GestaoRio de JaneiroBrazil22793-080
    18CEHONSalvadorBrazil45995-000
    19Hospital de Base de São José do Rio PretoSão José do Rio PretoBrazil15090-000
    20Clinica Sao GermanoSão PauloBrazil01455-010
    21HCFMUSPSão PauloBrazil05403-010
    22Tom Baker Cancer CentreCalgaryAlbertaCanadaT2N 4N2
    23Cross Cancer InstituteEdmontonAlbertaCanadaT6G 1Z2
    24The Gordon & Leslie Diamond Health Care CenterVancouverBritish ColumbiaCanadaV5Z 1M9
    25QEII Health Sciences CentreHalifaxNova ScotiaCanadaB3H 1V7
    26Victoria HospitalLondonOntarioCanadaN6A 5W9
    27Princess Margaret HospitalTorontoOntarioCanadaM5G 1X6
    28CHU de Québec -L'Hôtel-Dieu de QuébecQuébecQuebecCanadaG1R 2J6
    29Fakultni nemocnice BrnoBrnoCzechia625 00
    30Fakultni nemocnice Hradec KraloveHradec KraloveCzechia500 05
    31Fakultní nemocnice OlomoucOlomoucCzechia779 00
    32Fakultni nemocnice OstravaOstravaCzechia70852
    33Fakultni nemocnice Plzen, Hemato-onkologicke oddeleniPlzenCzechia304 60
    34Fakultni nemocnice Kralovske VinohradyPraha 10Czechia100 34
    35Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologiePraha 2Czechia128 08
    36CHU Caen - Côte de NacreCaenFrance14033
    37Hopital Claude HuriezLille CedexFrance59000
    38CHU de Nantes hôtel-DieuNantes Cedex 1France44093
    39CHU de BoreauxPessacFrance33604
    40Centre hospitalier Lyon-SudPierre-BéniteFrance69495
    41CHU Poitiers - Hôpital la MilétriePoitiersFrance86021
    42CHU Nancy BraboisVandoeuvre Les NancyFrance54511
    43Alexandra General Hospital of AthensAthens AtticaGreece115 28
    44Hillel Yaffe Medical Center - OncologyHaderaIsrael38100
    45Rambam Med.Center - Hematology InstituteHaifaIsrael31096
    46Carmel Medical CenterHaifaIsrael3436212
    47Hadassah Medical CenterJerusalemIsrael91120
    48Rabin Medical Center, Beilinson CampusPetah TikvaIsrael49100
    49Sheba Medical Center Tel HashomerRamat GanIsrael52621
    50Tel Aviv Sourasky Medical CenterTel AvivIsrael64239
    51Policlinico Sant'Orsola MalpighiBolognaItaly40138
    52Fondazione IRCCS Istituto Nazionale dei TumoriMilanoItaly20133
    53Ospedale Villa Sofia-CervelloPalermoItaly90146
    54Fondazione IRCCS Policlinico San MatteoPaviaItaly27100
    55Azienda USL di PiacenzaPiacenzaItaly29121
    56Università di Roma La SapienzaRomaItaly00161
    57Policlinico Universitario Agostino GemelliRomaItaly00168
    58A.O.U. Città della Salute e della ScienzaTorinoItaly10126
    59Fukuoka University HospitalFukuokaJapan814-0180
    60Chugoku Central HospitalFukuyamaJapan720-0001
    61Ogaki Municipal HospitalGifuJapan503-8502
    62Gunma University HospitalGunmaJapan371-0034
    63Kobe City Medical Center General HospitalHyogoJapan650-0047
    64Iwate Medical University HospitalIwateJapan020-8505
    65University Hospital Kyoto Perfectural University of MedicineKyotoJapan602-8566
    66Matsuyama Red Cross HospitalMatsuyamaJapan790-8524
    67Japanese Red Cross Nagoya Daini HospitalNagoyaJapan466-8650
    68Nagoya City University HospitalNagoyaJapan467-8602
    69Niigata Cancer Center HospitalNiigataJapan951-8566
    70National Hospital Organization Okayama Medical CenterOkayamaJapan701-1192
    71Osaka University HospitalOsakaJapan565-0871
    72National Hospital Organization Sendai Medical CenterSendai-CityJapan983-8520
    73National Hospital Organization Shibukawa Medical CenterShibukawaJapan377-0280
    74Japanese Red Cross Medical CenterShibuyaJapan150-8935
    75Pusan National University HospitalBusanKorea, Republic of49241
    76National Cancer CenterGoyang-SiKorea, Republic of10408
    77Gachon University Gil Medical CenterIncheonKorea, Republic of21565
    78Severance HospitalSeoulKorea, Republic of03722
    79Asan Medical CenterSeoulKorea, Republic of05505
    80Samsung Medical CenterSeoulKorea, Republic of06351
    81The Catholic University of Korea, Seoul St. Mary's HospitalSeoulKorea, Republic of06591
    82Ulsan University HospitalUlsanKorea, Republic of44033
    83Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. MarkiewiczaBrzozowPoland36-200
    84Szpital Uniwersytecki nr 2 im. Jana Biziela w BydgoszczyBydgoszczPoland85-168
    85Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali MiejskichChorzówPoland41-500
    86Szpitale Pomorskie Sp. z o.o.GdyniaPoland81-519
    87Szpital Uniwersytecki w KrakowieKrakowPoland31-501
    88Wojewodzki Szpital Specjalistyczny w LegnicyLegnicaPoland59-220
    89Samodzielny Publiczny Szpital Kliniczny nr 1 w LublinieLublinPoland20-081
    90Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola MarcinkowskiegoPoznanPoland60-569
    91Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut BadawczyWarszawaPoland02-781
    92Emergency Hospital of DzerzhinskDzerzhinskRussian Federation606019
    93Ekaterinburg City Clinical Hospital # 7EkaterinburgRussian Federation620137
    94S.P. Botkin Moscow City Clinical HospitalMoscowRussian Federation125284
    95City Clinical Hospital # 40MoscowRussian Federation129301
    96Nizhniy Novgorod Region Clinical HospitalNizny NovgorodRussian Federation603126
    97Penza Regional Oncology DispensaryPenzaRussian Federation440071
    98Ryazan Regional Clinical HospitalRyazanRussian Federation390039
    99Saint Petersburg City Hospital #15Saint-PetersburgRussian Federation123182
    100Samara Region Clinical HospitalSamaraRussian Federation443095
    101Clinical Research Institute of Hematology and TransfusiologySt-PetersburgRussian Federation191024
    102St.-Petersburg City Clinical Hospital nr 31St. PetersburgRussian Federation197110
    103Oncology Dispensary of Komi RepublicSyktyvkarRussian Federation167904
    104Hosp. Univ. Germans Trias I PujolBadalonaSpain08916
    105Hosp. Clinic I Provincial de BarcelonaBarcelonaSpain08036
    106Hosp. Univ. Dr. Josep TruetaGironaSpain17007
    107Hosp. Univ. Virgen de Las NievesGranadaSpain18014
    108Hosp. Univ. de CanariasLa LagunaSpain38320
    109Hosp. de LeonLeonSpain24080
    110Hosp. Gral. Univ. Gregorio MarañonMadridSpain28007
    111Hosp. Univ. Infanta LeonorMadridSpain28031
    112Hosp. Univ. 12 de OctubreMadridSpain28041
    113Clinica Univ. de NavarraPamplonaSpain31008
    114Hosp. Quiron Madrid PozueloPozuelo de AlarconSpain28223
    115Hosp. Clinico Univ. de SalamancaSalamancaSpain37007
    116Hosp. Univ. Dr. PesetValenciaSpain46017
    117Falu LasarettFalunSweden79182
    118Helsingborgs lasarettHelsingborgSweden25187
    119Karolinska University Hospital, HuddingeHuddingeSweden141 86
    120Skanes universitetssjukhusLundSweden222 41
    121Norrlands University HospitalUmeaSweden907 46
    122Akademiska SjukhusetUppsalaSwedenSE-751 85
    123Chang-Hua Christian HospitalChanghuaTaiwan50006
    124China Medical University HospitalTaichung CityTaiwan40447
    125Taichung Veterans General HospitalTaichung,Taiwan40705
    126National Cheng Kung University HospitalTainanTaiwan704
    127National Taiwan University HospitalTaipeiTaiwan10048
    128Chang Gung Memorial HospitalTaoyuanTaiwan33305
    129Communal Nonprofit Enterprise 'Cherkasy Regional Oncology Dispensary Of Cherkasy Regional Council'CherkasyUkraine18009
    130Dnepropetrovsk City Clinical Hospital #4, Regional Hematology CenterDnepropetrovskUkraine49102
    131Ivano-Frankivsk Regional Clinical HospitalIvano-FrankivskUkraine76008
    132SI Grigoriev Institute for Medical Radiology National Academy of Medical Science of UkraineKharkivUkraine61024
    133National Cancer Institute, Dept. of chemotherapy of hemoblastosisKievUkraine03022
    134Kiev Marrow Transplantation Center, Bone Marrow Transplantation DepartmentKievUkraine03115
    135State Institution 'National Scientific Center for Radiation Medicine of NAMS of Ukraine'KievUkraine03115
    136Institute of Blood Pathology and Transfusion Medicine of AMS of UkraineLvivUkraine79044
    137Mykolaiv Regional Clinical HospitalMykolaivUkraine54000
    138Ukrainian Medical Stomatological Academy, Poltava Regional Clinical HospitalPoltavaUkraine36011
    139Blackpool Victoria HospitalBlackpoolUnited KingdomFY3 8NR
    140Royal Bournemouth HospitalBournemouthUnited KingdomBH7 7DW
    141Leicester Royal Infirmary - HaematologyLeicesterUnited KingdomLE1 5WW
    142St Bartholomew's HospitalLondonUnited KingdomEC1A 7BE
    143Guy's & St Thomas HospitalLondonUnited KingdomSE1 9RT
    144Christie Hospital NHS TrustManchesterUnited KingdomM20 9BX
    145Nottingham City HospitalNottinghamUnited KingdomNG5 1PB
    146Royal Marsden HospitalSurreyUnited KingdomSM2 5PT
    147New Cross HospitalWolverhamptonUnited KingdomWV10 0QP

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT03277105
    Other Study ID Numbers:
    • CR108342
    • 2017-000206-38
    • 54767414MMY3012
    First Posted:
    Sep 8, 2017
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Period Title: Overall Study
    STARTED259263
    Safety Analysis Set258260
    COMPLETED00
    NOT COMPLETED259263

    Baseline Characteristics

    Arm/Group TitleDaratumumab IVDaratumumab SCTotal
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Total of all reporting groups
    Overall Participants259263522
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    66.8
    (10.16)
    65.3
    (9.11)
    66.1
    (9.66)
    Sex: Female, Male (Count of Participants)
    Female
    110
    42.5%
    127
    48.3%
    237
    45.4%
    Male
    149
    57.5%
    136
    51.7%
    285
    54.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    9
    3.5%
    14
    5.3%
    23
    4.4%
    Not Hispanic or Latino
    227
    87.6%
    225
    85.6%
    452
    86.6%
    Unknown or Not Reported
    23
    8.9%
    24
    9.1%
    47
    9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    0.4%
    1
    0.2%
    Asian
    40
    15.4%
    32
    12.2%
    72
    13.8%
    Native Hawaiian or Other Pacific Islander
    1
    0.4%
    0
    0%
    1
    0.2%
    Black or African American
    5
    1.9%
    9
    3.4%
    14
    2.7%
    White
    201
    77.6%
    207
    78.7%
    408
    78.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    12
    4.6%
    14
    5.3%
    26
    5%
    Region of Enrollment (Count of Participants)
    AUSTRALIA
    15
    5.8%
    13
    4.9%
    28
    5.4%
    BRAZIL
    10
    3.9%
    15
    5.7%
    25
    4.8%
    CANADA
    16
    6.2%
    20
    7.6%
    36
    6.9%
    CZECH REPUBLIC
    20
    7.7%
    16
    6.1%
    36
    6.9%
    FRANCE
    6
    2.3%
    10
    3.8%
    16
    3.1%
    GREECE
    1
    0.4%
    6
    2.3%
    7
    1.3%
    ISRAEL
    5
    1.9%
    8
    3%
    13
    2.5%
    ITALY
    10
    3.9%
    16
    6.1%
    26
    5%
    JAPAN
    24
    9.3%
    18
    6.8%
    42
    8%
    POLAND
    39
    15.1%
    26
    9.9%
    65
    12.5%
    RUSSIAN FEDERATION
    28
    10.8%
    27
    10.3%
    55
    10.5%
    SOUTH KOREA
    7
    2.7%
    4
    1.5%
    11
    2.1%
    SPAIN
    14
    5.4%
    12
    4.6%
    26
    5%
    SWEDEN
    18
    6.9%
    18
    6.8%
    36
    6.9%
    TAIWAN
    6
    2.3%
    8
    3%
    14
    2.7%
    UKRAINE
    22
    8.5%
    25
    9.5%
    47
    9%
    UNITED KINGDOM
    16
    6.2%
    17
    6.5%
    33
    6.3%
    UNITED STATES
    2
    0.8%
    4
    1.5%
    6
    1.1%
    Stage of Disease (ISS) (Count of Participants)
    Stage I
    94
    36.3%
    82
    31.2%
    176
    33.7%
    Stage II
    89
    34.4%
    101
    38.4%
    190
    36.4%
    Stage III
    76
    29.3%
    79
    30%
    155
    29.7%
    Data missing or Unknown
    0
    0%
    1
    0.4%
    1
    0.2%

    Outcome Measures

    1. Primary Outcome
    TitleOverall Response Rate (ORR)
    DescriptionORR 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 milligram (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.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all the randomized participants.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants259263
    Number (95% Confidence Interval) [percentage of participants]
    39.4
    15.2%
    43.3
    16.5%
    2. Primary Outcome
    TitleMaximum Trough Concentration (Ctrough) of Daratumumab
    DescriptionMaximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
    Time FramePredose on Cycle 3 Day 1 (each cycle of 28 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetics (PK) population included participants who received at least 1 administration of study drug and had at least 1 pharmacokinetics sample concentration value after the first dose administration. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants150157
    Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]
    525
    (227)
    611
    (318)
    3. Secondary Outcome
    TitlePercentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)
    DescriptionPercentage of participants with treatment-emergent infusion-related reactions were reported.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Safety population included all randomized participants who received at least 1 dose of study drug.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants258260
    Number (95% Confidence Interval) [percentage of participants]
    34.5
    13.3%
    12.7
    4.8%
    4. Secondary Outcome
    TitleProgression Free Survival (PFS)
    DescriptionPFS 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 grams 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.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all the randomized participants.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants259263
    Median (95% Confidence Interval) [months]
    6.08
    5.62
    5. Secondary Outcome
    TitlePercentage of Participants With Very Good Partial Response (VGPR) or Better
    DescriptionVGPR 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.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all the randomized participants.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants259263
    Number (95% Confidence Interval) [percentage of participants]
    20.8
    8%
    21.7
    8.3%
    6. Secondary Outcome
    TitlePercentage of Participants With Complete Response (Including sCR) or Better
    DescriptionCR 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.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all the randomized participants.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants259263
    Number (95% Confidence Interval) [percentage of participants]
    4.6
    1.8%
    3.0
    1.1%
    7. Secondary Outcome
    TitleTime to Next Therapy
    DescriptionTime to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all the randomized participants.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants259263
    Median (95% Confidence Interval) [months]
    9.30
    8.80
    8. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all the randomized participants.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants259263
    Median (95% Confidence Interval) [months]
    NA
    NA
    9. Secondary Outcome
    TitlePatient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ)
    DescriptionModified-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 FrameCycle 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)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all the randomized participants. Here, 'n' (number of participants analyzed) signifies the number of participants analyzed at a specified time point.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants259263
    Cycle 1 Day 8
    70.5
    (15.98)
    76.9
    (14.64)
    Cycle 1 Day 15
    72.1
    (16.72)
    78.8
    (14.95)
    Cycle 1 Day 22
    72.8
    (16.20)
    78.7
    (15.75)
    Cycle 2 Day 1
    74.2
    (16.44)
    79.7
    (16.58)
    Cycle 2 Day 8
    74.8
    (15.57)
    80.1
    (17.24)
    Cycle 2 Day 15
    74.3
    (16.94)
    80.0
    (17.37)
    Cycle 2 Day 22
    75.2
    (16.47)
    79.3
    (18.65)
    Cycle 3 Day 1
    76.0
    (17.39)
    80.4
    (17.78)
    Cycle 4 Day 1
    76.6
    (17.22)
    79.5
    (19.88)
    Cycle 5 Day 1
    77.1
    (17.11)
    79.6
    (18.95)
    Cycle 6 Day 1
    76.1
    (17.79)
    81.9
    (18.34)
    Cycle 7 Day 1
    78.6
    (16.01)
    85.0
    (16.87)
    Cycle 8 Day 1
    79.2
    (15.54)
    85.0
    (15.18)
    Cycle 9 Day 1
    79.8
    (15.27)
    85.2
    (15.03)
    Cycle 10 Day 1
    79.4
    (14.73)
    85.8
    (13.31)
    Cycle 11 Day 1
    79.1
    (15.55)
    84.8
    (13.50)
    Cycle 12 Day 1
    80.3
    (15.88)
    85.4
    (14.70)
    Cycle 13 Day 1
    79.6
    (16.57)
    84.4
    (15.09)
    Cycle 14 Day 1
    80.6
    (14.62)
    83.5
    (15.54)
    Cycle 15 Day 1
    80.2
    (15.22)
    86.2
    (13.51)
    Cycle 16 Day 1
    79.4
    (14.84)
    88.5
    (13.10)
    Cycle 17 Day 1
    79.0
    (14.34)
    90.9
    (11.26)
    Cycle 18 Day 1
    84.8
    (14.13)
    91.4
    (11.57)
    Cycle 19 Day 1
    92.9
    (10.10)
    89.3
    (13.36)
    Cycle 20 Day 1
    86.6
    (18.53)
    Cycle 21 Day 1
    84.5
    (20.93)
    Cycle 22 Day 1
    96.4
    10. Secondary Outcome
    TitleDuration of Response
    DescriptionDuration 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 FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Participants analyzed included responders (PR or better) in ITT analysis set.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants102114
    Median (95% Confidence Interval) [months]
    10.64
    11.17
    11. Secondary Outcome
    TitleTime to Partial Response (PR) or Better
    DescriptionTime to PR or better was defined as the time from randomization until onset of first response of PR or better.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Participants analyzed included responders (PR or better) in ITT analysis set.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants102114
    Median (Full Range) [months]
    1.02
    1.02
    12. Secondary Outcome
    TitleTime to Very Good Partial Response (VGPR) or Better
    DescriptionTime to VGPR or better was defined as the time from randomization until onset of first VGPR or better.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Participants analyzed included responders (VGPR or better) in ITT analysis set.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants5457
    Median (Full Range) [months]
    1.91
    1.94
    13. Secondary Outcome
    TitleTime to Complete Response (CR) or Better
    DescriptionTime to CR or better was defined as the time from randomization until onset of first CR or better.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Participants analyzed included responders (CR or better) in ITT analysis set.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    Measure Participants128
    Median (Full Range) [months]
    6.42
    7.39

    Adverse Events

    Time FrameUp to 2 years
    Adverse Event Reporting Description Safety population included all randomized participants who received at least 1 dose of study drug.
    Arm/Group TitleDaratumumab IVDaratumumab SC
    Arm/Group DescriptionParticipants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.Participants received daratumumab 1800 mg subcutaneous injection (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 thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
    All Cause Mortality
    Daratumumab IVDaratumumab SC
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total77/258 (29.8%) 73/260 (28.1%)
    Serious Adverse Events
    Daratumumab IVDaratumumab SC
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total76/258 (29.5%) 68/260 (26.2%)
    Blood and lymphatic system disorders
    Anaemia4/258 (1.6%) 5/260 (1.9%)
    Disseminated Intravascular Coagulation1/258 (0.4%) 0/260 (0%)
    Febrile Neutropenia2/258 (0.8%) 1/260 (0.4%)
    Hyperviscosity Syndrome0/258 (0%) 1/260 (0.4%)
    Neutropenia1/258 (0.4%) 0/260 (0%)
    Thrombocytopenia4/258 (1.6%) 3/260 (1.2%)
    Cardiac disorders
    Acute Coronary Syndrome1/258 (0.4%) 0/260 (0%)
    Angina Pectoris1/258 (0.4%) 0/260 (0%)
    Atrial Fibrillation0/258 (0%) 1/260 (0.4%)
    Atrioventricular Block Complete1/258 (0.4%) 0/260 (0%)
    Cardiac Failure1/258 (0.4%) 1/260 (0.4%)
    Cardiac Failure Chronic0/258 (0%) 1/260 (0.4%)
    Cardiopulmonary Failure0/258 (0%) 1/260 (0.4%)
    Myocardial Infarction2/258 (0.8%) 0/260 (0%)
    Tachycardia0/258 (0%) 1/260 (0.4%)
    Gastrointestinal disorders
    Diarrhoea1/258 (0.4%) 1/260 (0.4%)
    Gastrointestinal Haemorrhage1/258 (0.4%) 0/260 (0%)
    Gingival Bleeding0/258 (0%) 1/260 (0.4%)
    Ileus1/258 (0.4%) 0/260 (0%)
    Inguinal Hernia1/258 (0.4%) 0/260 (0%)
    Nausea2/258 (0.8%) 1/260 (0.4%)
    Oesophageal Varices Haemorrhage0/258 (0%) 1/260 (0.4%)
    Small Intestinal Obstruction0/258 (0%) 1/260 (0.4%)
    Subileus1/258 (0.4%) 0/260 (0%)
    Vomiting2/258 (0.8%) 0/260 (0%)
    General disorders
    Asthenia0/258 (0%) 2/260 (0.8%)
    Chest Discomfort1/258 (0.4%) 0/260 (0%)
    Chest Pain0/258 (0%) 1/260 (0.4%)
    Fatigue2/258 (0.8%) 1/260 (0.4%)
    General Physical Health Deterioration5/258 (1.9%) 4/260 (1.5%)
    Performance Status Decreased0/258 (0%) 1/260 (0.4%)
    Pyrexia4/258 (1.6%) 4/260 (1.5%)
    Hepatobiliary disorders
    Hyperbilirubinaemia1/258 (0.4%) 0/260 (0%)
    Infections and infestations
    Bacteraemia1/258 (0.4%) 0/260 (0%)
    Bronchitis1/258 (0.4%) 1/260 (0.4%)
    Campylobacter Gastroenteritis1/258 (0.4%) 0/260 (0%)
    Furuncle0/258 (0%) 1/260 (0.4%)
    Hepatitis B Reactivation1/258 (0.4%) 0/260 (0%)
    Infection1/258 (0.4%) 0/260 (0%)
    Influenza2/258 (0.8%) 3/260 (1.2%)
    Listeriosis0/258 (0%) 1/260 (0.4%)
    Lower Respiratory Tract Infection3/258 (1.2%) 3/260 (1.2%)
    Lung Infection2/258 (0.8%) 5/260 (1.9%)
    Mastoiditis1/258 (0.4%) 0/260 (0%)
    Meningitis Cryptococcal0/258 (0%) 1/260 (0.4%)
    Meningitis Pneumococcal1/258 (0.4%) 0/260 (0%)
    Neutropenic Sepsis0/258 (0%) 1/260 (0.4%)
    Pneumocystis Jirovecii Pneumonia2/258 (0.8%) 0/260 (0%)
    Pneumonia11/258 (4.3%) 7/260 (2.7%)
    Respiratory Tract Infection1/258 (0.4%) 2/260 (0.8%)
    Sepsis4/258 (1.6%) 3/260 (1.2%)
    Septic Shock4/258 (1.6%) 3/260 (1.2%)
    Staphylococcal Sepsis1/258 (0.4%) 0/260 (0%)
    Upper Respiratory Tract Infection1/258 (0.4%) 0/260 (0%)
    Urinary Tract Infection3/258 (1.2%) 0/260 (0%)
    Injury, poisoning and procedural complications
    Femoral Neck Fracture0/258 (0%) 1/260 (0.4%)
    Femur Fracture2/258 (0.8%) 1/260 (0.4%)
    Humerus Fracture0/258 (0%) 2/260 (0.8%)
    Upper Limb Fracture0/258 (0%) 1/260 (0.4%)
    Investigations
    General Physical Condition Abnormal0/258 (0%) 1/260 (0.4%)
    Oxygen Saturation Decreased0/258 (0%) 1/260 (0.4%)
    Metabolism and nutrition disorders
    Hypercalcaemia4/258 (1.6%) 2/260 (0.8%)
    Hyperglycaemia2/258 (0.8%) 0/260 (0%)
    Hypernatraemia1/258 (0.4%) 0/260 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia0/258 (0%) 1/260 (0.4%)
    Back Pain1/258 (0.4%) 2/260 (0.8%)
    Bone Pain2/258 (0.8%) 5/260 (1.9%)
    Muscular Weakness1/258 (0.4%) 0/260 (0%)
    Neck Pain0/258 (0%) 1/260 (0.4%)
    Pain in Extremity0/258 (0%) 2/260 (0.8%)
    Pathological Fracture0/258 (0%) 1/260 (0.4%)
    Spinal Pain1/258 (0.4%) 0/260 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of Colon1/258 (0.4%) 0/260 (0%)
    Intestinal Adenocarcinoma0/258 (0%) 1/260 (0.4%)
    Plasmacytoma1/258 (0.4%) 0/260 (0%)
    Prostate Cancer Recurrent0/258 (0%) 1/260 (0.4%)
    Tumour Associated Fever0/258 (0%) 1/260 (0.4%)
    Nervous system disorders
    Brain Oedema1/258 (0.4%) 0/260 (0%)
    Cerebral Infarction0/258 (0%) 1/260 (0.4%)
    Cerebrovascular Accident0/258 (0%) 1/260 (0.4%)
    Cerebrovascular Insufficiency0/258 (0%) 1/260 (0.4%)
    Monoparesis1/258 (0.4%) 0/260 (0%)
    Peripheral Sensory Neuropathy1/258 (0.4%) 0/260 (0%)
    Spinal Cord Compression0/258 (0%) 1/260 (0.4%)
    Syncope0/258 (0%) 1/260 (0.4%)
    Transient Ischaemic Attack1/258 (0.4%) 1/260 (0.4%)
    Psychiatric disorders
    Confusional State2/258 (0.8%) 0/260 (0%)
    Renal and urinary disorders
    Acute Kidney Injury4/258 (1.6%) 4/260 (1.5%)
    Haematuria0/258 (0%) 2/260 (0.8%)
    Myeloma Cast Nephropathy0/258 (0%) 1/260 (0.4%)
    Renal Failure1/258 (0.4%) 2/260 (0.8%)
    Reproductive system and breast disorders
    Pelvic Pain1/258 (0.4%) 0/260 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm1/258 (0.4%) 0/260 (0%)
    Cough0/258 (0%) 1/260 (0.4%)
    Epistaxis0/258 (0%) 1/260 (0.4%)
    Hypoxia1/258 (0.4%) 0/260 (0%)
    Pulmonary Embolism1/258 (0.4%) 0/260 (0%)
    Pulmonary Thrombosis1/258 (0.4%) 0/260 (0%)
    Respiratory Distress0/258 (0%) 1/260 (0.4%)
    Respiratory Failure0/258 (0%) 2/260 (0.8%)
    Vascular disorders
    Circulatory Collapse1/258 (0.4%) 0/260 (0%)
    Deep Vein Thrombosis0/258 (0%) 1/260 (0.4%)
    Hypertension1/258 (0.4%) 1/260 (0.4%)
    Hypotension1/258 (0.4%) 0/260 (0%)
    Other (Not Including Serious) Adverse Events
    Daratumumab IVDaratumumab SC
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total204/258 (79.1%) 208/260 (80%)
    Blood and lymphatic system disorders
    Anaemia58/258 (22.5%) 67/260 (25.8%)
    Leukopenia10/258 (3.9%) 18/260 (6.9%)
    Lymphopenia17/258 (6.6%) 19/260 (7.3%)
    Neutropenia34/258 (13.2%) 50/260 (19.2%)
    Thrombocytopenia48/258 (18.6%) 46/260 (17.7%)
    Gastrointestinal disorders
    Constipation20/258 (7.8%) 14/260 (5.4%)
    Diarrhoea27/258 (10.5%) 39/260 (15%)
    Nausea26/258 (10.1%) 21/260 (8.1%)
    Vomiting18/258 (7%) 14/260 (5.4%)
    General disorders
    Asthenia13/258 (5%) 12/260 (4.6%)
    Chills32/258 (12.4%) 15/260 (5.8%)
    Fatigue25/258 (9.7%) 28/260 (10.8%)
    Oedema Peripheral13/258 (5%) 9/260 (3.5%)
    Pyrexia30/258 (11.6%) 31/260 (11.9%)
    Infections and infestations
    Nasopharyngitis16/258 (6.2%) 18/260 (6.9%)
    Upper Respiratory Tract Infection25/258 (9.7%) 35/260 (13.5%)
    Metabolism and nutrition disorders
    Hypokalaemia15/258 (5.8%) 11/260 (4.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia15/258 (5.8%) 19/260 (7.3%)
    Back Pain31/258 (12%) 27/260 (10.4%)
    Bone Pain8/258 (3.1%) 14/260 (5.4%)
    Musculoskeletal Chest Pain14/258 (5.4%) 16/260 (6.2%)
    Pain in Extremity11/258 (4.3%) 15/260 (5.8%)
    Nervous system disorders
    Headache22/258 (8.5%) 13/260 (5%)
    Psychiatric disorders
    Insomnia13/258 (5%) 14/260 (5.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough33/258 (12.8%) 22/260 (8.5%)
    Dyspnoea28/258 (10.9%) 14/260 (5.4%)
    Nasal Congestion13/258 (5%) 10/260 (3.8%)
    Vascular disorders
    Hypertension22/258 (8.5%) 13/260 (5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.

    Results Point of Contact

    Name/TitleGlobal Medical Head
    OrganizationJanssen Research & Development, LLC
    Phone844-434-4210
    EmailClinicalTrialDisclosure@its.jnj.com
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT03277105
    Other Study ID Numbers:
    • CR108342
    • 2017-000206-38
    • 54767414MMY3012
    First Posted:
    Sep 8, 2017
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Dec 1, 2021