A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma
A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
3 other identifiers
interventional
522
18 countries
146
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-myeloma
Started Oct 2017
146 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 7, 2017
CompletedFirst Posted
Study publicly available on registry
September 8, 2017
CompletedStudy Start
First participant enrolled
October 27, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 27, 2019
CompletedResults Posted
Study results publicly available
July 27, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 12, 2024
CompletedApril 29, 2025
April 1, 2025
1.7 years
September 7, 2017
June 19, 2020
April 25, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Overall Response Rate (ORR)
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.
Up to 1 year 8 months
Maximum Trough Concentration (Ctrough) of Daratumumab
Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Predose on Cycle 3 Day 1 (each cycle of 28 days)
Secondary Outcomes (11)
Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)
Up to 3 years
Progression Free Survival (PFS)
Up to 3 years
Percentage of Participants With Very Good Partial Response (VGPR) or Better
Up to 3 years
Percentage of Participants With Complete Response (Including sCR) or Better
Up to 3 years
Time to Next Therapy
Up to 3 years
- +6 more secondary outcomes
Study Arms (2)
Dara SC
EXPERIMENTALParticipants 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
ACTIVE COMPARATORParticipants 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.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (146)
Dana Farber Cancer Institute
Boston, Massachusetts, 02215-5418, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Royal Prince Alfred Hospital
Camperdown, 2050, Australia
St Vincents Hospital Melbourne
Fitzroy, 3065, Australia
Alfred Health
Melbourne, 3004, Australia
Fiona Stanley Hospital
Murdoch, 6150, Australia
Sir Charles Gairdner Hospital
Nedlands, 6009, Australia
Calvary Mater Newcastle Hospital
Waratah, 2298, Australia
The Queen Elizabeth Hospital
Woodville South, 5011, Australia
Princess Alexandra Hospital
Woolloongabba, 4102, Australia
Fundacao Pio XII
Barretos, 14784-400, Brazil
Centro de Pesquisa e Ensino em Oncologia de Santa Catarina CEPEN
Florianópolis, 88034-000, Brazil
Fundacao Doutor Amaral Carvalho
Jaú, 17210 080, Brazil
Instituto Joinvilense de Hematologia e Oncologia Ltda Centro de Hematologia e Oncologia
Joinville, 89201-260, Brazil
Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo
Passo Fundo, 99010-090, Brazil
Hospital das Clinicas de Porto Alegre
Porto Alegre, 90035-903, Brazil
Instituto de Educacao, Pesquisa e Gestao em Saude
Rio de Janeiro, 22775-001, Brazil
CEHON
Salvador, 45995-000, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base
São José do Rio Preto, 15090-000, Brazil
Clinica Sao Germano
São Paulo, 01455 010, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da USP
São Paulo, 05403-010, Brazil
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
The Gordon & Leslie Diamond Health Care Center
Vancouver, British Columbia, V5Z 1M9, Canada
QEII Health Sciences Centre
Halifax, Nova Scotia, B3H 1V7, Canada
Victoria Hospital
London, Ontario, N6A 5W9, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G 1X6, Canada
CHU de Quebec L Hotel Dieu de Quebec
Québec, Quebec, G1R 2J6, Canada
Fakultni nemocnice Brno
Brno, 625 00, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Fakultni nemocnice Olomouc
Olomouc, 779 00, Czechia
Fakultni Nemocnice Ostrava
Ostrava, 70852, Czechia
Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
Pilsen, 323 00, Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, 100 34, Czechia
Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
Prague, 128 08, Czechia
CHU Caen - Côte de Nacre
Caen, 14033, France
Hopital Claude Huriez
Lille, 59000, France
CHU de Nantes hotel Dieu
Nantes, 44093, France
CHU de Boreaux
Pessac, 33604, France
Centre hospitalier Lyon-Sud
Pierre-Bénite, 69495, France
CHU Poitiers - Hopital la Miletrie
Poitiers, 86021, France
CHU Nancy Brabois
Vandœuvre-lès-Nancy, 54511, France
Alexandra General Hospital of Athens
Athens Attica, 115 28, Greece
Hillel Yaffe Medical Center - Oncology
Hadera, 38100, Israel
Rambam Med.Center - Hematology Institute
Haifa, 31096, Israel
Carmel Medical Center
Haifa, 3436212, Israel
Hadassah Medical Center
Jerusalem, 91120, Israel
Rabin Medical Center Beilinson Campus
Petah Tikva, 49100, Israel
Sheba Medical Center Tel Hashomer
Ramat Gan, 52621, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
Policlinico Sant'Orsola Malpighi
Bologna, 40138, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133, Italy
Ospedale Villa Sofia-Cervello
Palermo, 90146, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100, Italy
Azienda USL di Piacenza
Piacenza, 29121, Italy
Università di Roma La Sapienza
Roma, 00161, Italy
Policlinico Universitario Agostino Gemelli
Roma, 00168, Italy
A.O.U. Città della Salute e della Scienza
Torino, 10126, Italy
Fukuoka University Hospital
Fukuoka, 814-0180, Japan
Chugoku Central Hospital
Fukuyama, 720-0001, Japan
Ogaki Municipal Hospital
Gifu, 503-8502, Japan
Gunma University Hospital
Gunma, 371-0034, Japan
Kobe City Medical Center General Hospital
Kobe, 650 0047, Japan
University Hospital Kyoto Prefectural University of Medicine
Kyoto, 602-8566, Japan
Matsuyama Red Cross Hospital
Matsuyama, 790-8524, Japan
Japanese Red Cross Nagoya Daini Hospital
Nagoya, 466-8650, Japan
Nagoya City University Hospital
Nagoya, 467 8602, Japan
Niigata Cancer Center Hospital
Niigata, 951-8566, Japan
Iwate Medical University Hospital
Numakunai, 020-8505, Japan
National Hospital Organization Okayama Medical Center
Okayama, 701-1192, Japan
Osaka University Hospital
Osaka, 565-0871, Japan
National Hospital Organization Sendai Medical Center
Sendai, 983-8520, Japan
National Hospital Organization Shibukawa Medical Center
Shibukawa, 377-0280, Japan
Japanese Red Cross Medical Center
Shibuya City, 150-8935, Japan
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
Brzozów, 36-200, Poland
Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
Bydgoszcz, 85-168, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
Chorzów, 41-500, Poland
Szpitale Pomorskie Sp z o o
Gdynia, 81 519, Poland
Szpital Uniwersytecki w Krakowie
Krakow, 31 501, Poland
Wojewodzki Szpital Specjalistyczny w Legnicy
Legnica, 59-220, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, 20-081, Poland
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im Karola Marcinkowskiego
Poznan, 60 569, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
Warsaw, 02-781, Poland
Emergency Hospital of Dzerzhinsk
Dzerzhinsk, 606019, Russia
S.P. Botkin Moscow City Clinical Hospital
Moscow, 125284, Russia
City Clinical Hospital # 40
Moscow, 129301, Russia
Nizhniy Novgorod Region Clinical Hospital
Nizny Novgorod, 603126, Russia
Penza Regional Oncology Dispensary
Penza, 440071, Russia
Ryazan Regional Clinical Hospital
Ryazan, 390039, Russia
Saint Petersburg City Hospital #15
Saint Petersburg, 123182, Russia
Clinical Research Institute of Hematology and Transfusiology
Saint Petersburg, 191024, Russia
Samara Region Clinical Hospital
Samara, 443095, Russia
Oncology Dispensary of Komi Republic
Syktyvkar, 167904, Russia
Ekaterinburg City Clinical Hospital # 7
Yekaterinburg, 620137, Russia
Pusan National University Hospital
Busan, 49241, South Korea
National Cancer Center
Goyang-si, 10408, South Korea
Gachon University Gil Medical Center
Incheon, 21565, South Korea
Severance Hospital
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
The Catholic University of Korea Seoul St Marys Hospital
Seoul, 06591, South Korea
Ulsan University Hospital
Ulsan, 44033, South Korea
Hosp. Univ. Germans Trias I Pujol
Badalona, 08916, Spain
Hosp Clinic de Barcelona
Barcelona, 08036, Spain
Hosp. Univ. Dr. Josep Trueta
Girona, 17007, Spain
Hosp. Univ. Virgen de Las Nieves
Granada, 18014, Spain
Hosp. de Leon
León, 24008, Spain
Hosp. Gral. Univ. Gregorio Maranon
Madrid, 28007, Spain
Hosp. Univ. Infanta Leonor
Madrid, 28031, Spain
Hosp. Univ. 12 de Octubre
Madrid, 28041, Spain
Clinica Univ. de Navarra
Pamplona, 31008, Spain
Hosp. Quiron Madrid Pozuelo
Pozuelo de Alarcón, 28223, Spain
Hosp Clinico Univ de Salamanca
Salamanca, 37007, Spain
Hosp. Univ. de Canarias
San Cristóbal de La Laguna, 38320, Spain
Hosp. Univ. Dr. Peset
Valencia, 46017, Spain
Falu Lasarett
Falun, 79182, Sweden
Helsingborgs lasarett
Helsingborg, 25187, Sweden
Karolinska University Hospital Huddinge
Huddinge, 141 86, Sweden
Skanes universitetssjukhus
Lund, 222 41, Sweden
Norrlands University Hospital
Umeå, 907 46, Sweden
Akademiska Sjukhuset
Uppsala, SE-751 85, Sweden
Chang-Hua Christian Hospital
Changhua, 50006, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
National Cheng Kung University Hospital
Tainan, 704, Taiwan
National Taiwan University Hospital
Taipei, 10048, Taiwan
Chang Gung Memorial Hospital
Taoyuan District, 33305, Taiwan
Communal Nonprofit Enterprise 'Cherkasy Regional Oncology Dispensary Of Cherkasy Regional Council'
Cherkasy, 18009, Ukraine
Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center
Dnipro, 49102, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
Ivano-Frankivsk, 76008, Ukraine
SI Grigoriev Institute for Medical Radiology National Academy of Medical Science of Ukraine
Kharkiv, 61024, Ukraine
National Cancer Institute, Dept. of chemotherapy of hemoblastosis
Kiev, 03022, Ukraine
Kiev Marrow Transplantation Center, Bone Marrow Transplantation Department
Kiev, 03115, Ukraine
State Institution 'National Scientific Center for Radiation Medicine of NAMS of Ukraine'
Kiev, 03115, Ukraine
Institute of Blood Pathology and Transfusion Medicine of AMS of Ukraine
Lviv, 79044, Ukraine
Mykolaiv Regional Clinical Hospital
Mykolaiv, 54000, Ukraine
Ukrainian Medical Stomatological Academy, Poltava Regional Clinical Hospital
Poltava, 36011, Ukraine
Blackpool Victoria Hospital
Blackpool, FY3 8NR, United Kingdom
Royal Bournemouth Hospital
Bournemouth, BH7 7DW, United Kingdom
Leicester Royal Infirmary - Haematology
Leicester, LE1 5WW, United Kingdom
St Bartholomew's Hospital
London, EC1A 7BE, United Kingdom
Guys St Thomas Hospital
London, SE1 9RT, United Kingdom
Christie Hospital NHS Trust
Manchester, M20 9BX, United Kingdom
Nottingham City Hospital
Nottingham, NG5 1PB, United Kingdom
Royal Marsden Hospital
Surrey, SM2 5PT, United Kingdom
New Cross Hospital
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (6)
LaRoche JK, Lanier J, Alvarenga R, Collins M, Costelloe T, Chiau A, Whetherly H, De Soete W, Faludi J, Rens K. Climate footprint of industry-sponsored in-human clinical trials: life cycle assessments of clinical trials spanning multiple phases and disease areas. BMJ Open. 2025 Feb 19;15(2):e085364. doi: 10.1136/bmjopen-2024-085364.
PMID: 39971605DERIVEDLi X, Dosne AG, Perez Ruixo C, Perez Ruixo JJ. Pharmacodynamic-Mediated Drug Disposition (PDMDD) Model of Daratumumab Monotherapy in Patients with Multiple Myeloma. Clin Pharmacokinet. 2023 May;62(5):761-777. doi: 10.1007/s40262-023-01232-8. Epub 2023 Apr 6.
PMID: 37022569DERIVEDUsmani SZ, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis NJ, Flogegard M, Blade J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Lantz K, O'Rourke L, Heuck C, Delioukina M, Qin X, Nnane I, Qi M, Mateos MV. Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. 2022 Oct 1;107(10):2408-2417. doi: 10.3324/haematol.2021.279459.
PMID: 35354247DERIVEDIida S, Ishikawa T, Min CK, Kim K, Yeh SP, Usmani SZ, Mateos MV, Nahi H, Heuck C, Qin X, Parasrampuria DA, Gries KS, Qi M, Bahlis N, Ito S. Subcutaneous daratumumab in Asian patients with heavily pretreated multiple myeloma: subgroup analyses of the noninferiority, phase 3 COLUMBA study. Ann Hematol. 2021 Apr;100(4):1065-1077. doi: 10.1007/s00277-021-04405-2. Epub 2021 Feb 18.
PMID: 33599794DERIVEDUsmani SZ, Mateos MV, Hungria V, Iida S, Bahlis NJ, Nahi H, Magen H, Cavo M, Hulin C, White D, De Stefano V, Fastenau J, Slavcev M, Heuck C, Qin X, Pei H, Masterson T, Lantz K, Gries KS. Greater treatment satisfaction in patients receiving daratumumab subcutaneous vs. intravenous for relapsed or refractory multiple myeloma: COLUMBA clinical trial results. J Cancer Res Clin Oncol. 2021 Feb;147(2):619-631. doi: 10.1007/s00432-020-03365-w. Epub 2020 Aug 27.
PMID: 32852632DERIVEDMateos MV, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis N, Flogegard M, Blade J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Clemens PL, Masterson T, Lantz K, O'Rourke L, Heuck C, Qin X, Parasrampuria DA, Yuan Z, Xu S, Qi M, Usmani SZ. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020 May;7(5):e370-e380. doi: 10.1016/S2352-3026(20)30070-3. Epub 2020 Mar 23.
PMID: 32213342DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Medical Head
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 7, 2017
First Posted
September 8, 2017
Study Start
October 27, 2017
Primary Completion
June 27, 2019
Study Completion
January 12, 2024
Last Updated
April 29, 2025
Results First Posted
July 27, 2020
Record last verified: 2025-04