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

NCT ID: NCT03277105

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 522 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-27
• Study Completion Date: 2024-01-12

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dara SC

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Dara SC

Intervention Type: DRUG

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.

Dara IV

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

JNJ-54767414

Eligibility Criteria

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:

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

2. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Royal Prince Alfred Hospital

Camperdown, , Australia

St Vincents Hospital Melbourne

Fitzroy, , Australia

Alfred Health

Melbourne, , Australia

Fiona Stanley Hospital

Murdoch, , Australia

Sir Charles Gairdner Hospital

Nedlands, , Australia

Calvary Mater Newcastle Hospital

Waratah, , Australia

The Queen Elizabeth Hospital

Woodville South, , Australia

Princess Alexandra Hospital

Woolloongabba, , Australia

Fundacao Pio XII

Barretos, , Brazil

Centro de Pesquisa e Ensino em Oncologia de Santa Catarina CEPEN

Florianópolis, , Brazil

Fundacao Doutor Amaral Carvalho

Jaú, , Brazil

Instituto Joinvilense de Hematologia e Oncologia Ltda Centro de Hematologia e Oncologia

Joinville, , Brazil

Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo

Passo Fundo, , Brazil

Hospital das Clinicas de Porto Alegre

Porto Alegre, , Brazil

Instituto de Educacao, Pesquisa e Gestao em Saude

Rio de Janeiro, , Brazil

CEHON

Salvador, , Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base

São José do Rio Preto, , Brazil

Clinica Sao Germano

São Paulo, , Brazil

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, , Brazil

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

The Gordon & Leslie Diamond Health Care Center

Vancouver, British Columbia, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Victoria Hospital

London, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

CHU de Quebec L Hotel Dieu de Quebec

Québec, Quebec, Canada

Fakultni nemocnice Brno

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Fakultni Nemocnice Ostrava

Ostrava, , Czechia

Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni

Pilsen, , Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie

Prague, , Czechia

CHU Caen - Côte de Nacre

Caen, , France

Hopital Claude Huriez

Lille, , France

CHU de Nantes hotel Dieu

Nantes, , France

CHU de Boreaux

Pessac, , France

Centre hospitalier Lyon-Sud

Pierre-Bénite, , France

CHU Poitiers - Hopital la Miletrie

Poitiers, , France

CHU Nancy Brabois

Vandœuvre-lès-Nancy, , France

Alexandra General Hospital of Athens

Athens Attica, , Greece

Hillel Yaffe Medical Center - Oncology

Hadera, , Israel

Rambam Med.Center - Hematology Institute

Haifa, , Israel

Carmel Medical Center

Haifa, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Rabin Medical Center Beilinson Campus

Petah Tikva, , Israel

Sheba Medical Center Tel Hashomer

Ramat Gan, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Ospedale Villa Sofia-Cervello

Palermo, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Azienda USL di Piacenza

Piacenza, , Italy

Università di Roma La Sapienza

Roma, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

A.O.U. Città della Salute e della Scienza

Torino, , Italy

Fukuoka University Hospital

Fukuoka, , Japan

Chugoku Central Hospital

Fukuyama, , Japan

Ogaki Municipal Hospital

Gifu, , Japan

Gunma University Hospital

Gunma, , Japan

Kobe City Medical Center General Hospital

Kobe, , Japan

University Hospital Kyoto Prefectural University of Medicine

Kyoto, , Japan

Matsuyama Red Cross Hospital

Matsuyama, , Japan

Japanese Red Cross Nagoya Daini Hospital

Nagoya, , Japan

Nagoya City University Hospital

Nagoya, , Japan

Niigata Cancer Center Hospital

Niigata, , Japan

Iwate Medical University Hospital

Numakunai, , Japan

National Hospital Organization Okayama Medical Center

Okayama, , Japan

Osaka University Hospital

Osaka, , Japan

National Hospital Organization Sendai Medical Center

Sendai, , Japan

National Hospital Organization Shibukawa Medical Center

Shibukawa, , Japan

Japanese Red Cross Medical Center

Shibuya City, , Japan

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza

Brzozów, , Poland

Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy

Bydgoszcz, , Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

Chorzów, , Poland

Szpitale Pomorskie Sp z o o

Gdynia, , Poland

Szpital Uniwersytecki w Krakowie

Krakow, , Poland

Wojewodzki Szpital Specjalistyczny w Legnicy

Legnica, , Poland

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, , Poland

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im Karola Marcinkowskiego

Poznan, , Poland

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

Warsaw, , Poland

Emergency Hospital of Dzerzhinsk

Dzerzhinsk, , Russia

S.P. Botkin Moscow City Clinical Hospital

Moscow, , Russia

City Clinical Hospital # 40

Moscow, , Russia

Nizhniy Novgorod Region Clinical Hospital

Nizny Novgorod, , Russia

Penza Regional Oncology Dispensary

Penza, , Russia

Ryazan Regional Clinical Hospital

Ryazan, , Russia

Saint Petersburg City Hospital #15

Saint Petersburg, , Russia

Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, , Russia

Samara Region Clinical Hospital

Samara, , Russia

Oncology Dispensary of Komi Republic

Syktyvkar, , Russia

Ekaterinburg City Clinical Hospital # 7

Yekaterinburg, , Russia

Pusan National University Hospital

Busan, , South Korea

National Cancer Center

Goyang-si, , South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea Seoul St Marys Hospital

Seoul, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

Hosp. Univ. Germans Trias I Pujol

Badalona, , Spain

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp. Univ. Dr. Josep Trueta

Girona, , Spain

Hosp. Univ. Virgen de Las Nieves

Granada, , Spain

Hosp. de Leon

León, , Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Hosp. Univ. Infanta Leonor

Madrid, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Hosp. Univ. de Canarias

San Cristóbal de La Laguna, , Spain

Hosp. Univ. Dr. Peset

Valencia, , Spain

Falu Lasarett

Falun, , Sweden

Helsingborgs lasarett

Helsingborg, , Sweden

Karolinska University Hospital Huddinge

Huddinge, , Sweden

Skanes universitetssjukhus

Lund, , Sweden

Norrlands University Hospital

Umeå, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Chang-Hua Christian Hospital

Changhua, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Communal Nonprofit Enterprise 'Cherkasy Regional Oncology Dispensary Of Cherkasy Regional Council'

Cherkasy, , Ukraine

Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center

Dnipro, , Ukraine

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

SI Grigoriev Institute for Medical Radiology National Academy of Medical Science of Ukraine

Kharkiv, , Ukraine

National Cancer Institute, Dept. of chemotherapy of hemoblastosis

Kiev, , Ukraine

Kiev Marrow Transplantation Center, Bone Marrow Transplantation Department

Kiev, , Ukraine

State Institution 'National Scientific Center for Radiation Medicine of NAMS of Ukraine'

Kiev, , Ukraine

Institute of Blood Pathology and Transfusion Medicine of AMS of Ukraine

Lviv, , Ukraine

Mykolaiv Regional Clinical Hospital

Mykolaiv, , Ukraine

Ukrainian Medical Stomatological Academy, Poltava Regional Clinical Hospital

Poltava, , Ukraine

Blackpool Victoria Hospital

Blackpool, , United Kingdom

Royal Bournemouth Hospital

Bournemouth, , United Kingdom

Leicester Royal Infirmary - Haematology

Leicester, , United Kingdom

St Bartholomew's Hospital

London, , United Kingdom

Guys St Thomas Hospital

London, , United Kingdom

Christie Hospital NHS Trust

Manchester, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Royal Marsden Hospital

Surrey, , United Kingdom

New Cross Hospital

Wolverhampton, , United Kingdom

Countries

United States; Australia; Brazil; Canada; Czechia; France; Greece; Israel; Italy; Japan; Poland; Russia; South Korea; Spain; Sweden; Taiwan; Ukraine; United Kingdom

References

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000206-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54767414MMY3012

Identifier Type: OTHER

Identifier Source: secondary_id

CR108342

Identifier Type: -

Identifier Source: org_study_id