Clinical trial NCT03277105: A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-09-08
Enrollment: 522
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 1 year 8 months
measure: Maximum Trough Concentration (Ctrough) of Daratumumab
timeFrame: Predose on Cycle 3 Day 1 (each cycle of 28 days)
Secondary outcomes:
measure: Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)
timeFrame: Up to 3 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Percentage of Participants With Very Good Partial Response (VGPR) or Better
timeFrame: Up to 3 years
measure: Percentage of Participants With Complete Response (Including sCR) or Better
timeFrame: Up to 3 years
measure: Time to Next Therapy
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ)
timeFrame: 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)
measure: Duration of Response
timeFrame: Up to 3 years
measure: Time to Partial Response (PR) or Better
timeFrame: Up to 3 years
measure: Time to Very Good Partial Response (VGPR) or Better
timeFrame: Up to 3 years
measure: Time to Complete Response (CR) or Better
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
city: Melbourne
country: Australia
facility: Alfred Health
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Barretos
country: Brazil
facility: Fundacao Pio XII
city: Florianopolis
country: Brazil
facility: Centro de Pesquisa e Ensino em Oncologia de Santa Catarina CEPEN
city: Jau
country: Brazil
facility: Fundacao Doutor Amaral Carvalho
city: Joinville
country: Brazil
facility: Instituto Joinvilense de Hematologia e Oncologia Ltda Centro de Hematologia e Oncologia
city: Passo Fundo
country: Brazil
facility: Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Instituto de Educacao, Pesquisa e Gestao em Saude
city: Salvador
country: Brazil
facility: CEHON
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base
city: São Paulo
country: Brazil
facility: Clinica Sao Germano
city: São Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da USP
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: The Gordon & Leslie Diamond Health Care Center
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Québec
country: Canada
facility: CHU de Quebec L Hotel Dieu de Quebec
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Ostrava
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
city: Caen
country: France
facility: CHU Caen - Côte de Nacre
city: Lille Cedex
country: France
facility: Hopital Claude Huriez
city: Nantes Cedex 1
country: France
facility: CHU de Nantes hotel Dieu
city: Pessac
country: France
facility: CHU de Boreaux
city: Pierre-Bénite
country: France
facility: Centre hospitalier Lyon-Sud
city: Poitiers
country: France
facility: CHU Poitiers - Hopital la Miletrie
city: Vandoeuvre Les Nancy
country: France
facility: CHU Nancy Brabois
city: Athens Attica
country: Greece
facility: Alexandra General Hospital of Athens
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center - Oncology
city: Haifa
country: Israel
facility: Rambam Med.Center - Hematology Institute
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center Beilinson Campus
city: Ramat Gan
country: Israel
facility: Sheba Medical Center Tel Hashomer
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Palermo
country: Italy
facility: Ospedale Villa Sofia-Cervello
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Piacenza
country: Italy
facility: Azienda USL di Piacenza
city: Roma
country: Italy
facility: Università di Roma La Sapienza
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Fukuyama
country: Japan
facility: Chugoku Central Hospital
city: Gifu
country: Japan
facility: Ogaki Municipal Hospital
city: Gunma
country: Japan
facility: Gunma University Hospital
city: Iwate
country: Japan
facility: Iwate Medical University Hospital
city: Kobe City
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
city: Matsuyama
country: Japan
facility: Matsuyama Red Cross Hospital
city: Nagoya
country: Japan
facility: Japanese Red Cross Nagoya Daini Hospital
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Sendai-City
country: Japan
facility: National Hospital Organization Sendai Medical Center
city: Shibukawa
country: Japan
facility: National Hospital Organization Shibukawa Medical Center
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
city: Chorzow
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp z o o
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Legnica
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Legnicy
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im Karola Marcinkowskiego
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
city: Dzerzhinsk
country: Russian Federation
facility: Emergency Hospital of Dzerzhinsk
city: Ekaterinburg
country: Russian Federation
facility: Ekaterinburg City Clinical Hospital # 7
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 40
city: Nizny Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Clinical Hospital
city: Penza
country: Russian Federation
facility: Penza Regional Oncology Dispensary
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Hospital
city: Saint-Petersburg
country: Russian Federation
facility: Saint Petersburg City Hospital #15
city: Samara
country: Russian Federation
facility: Samara Region Clinical Hospital
city: St-Petersburg
country: Russian Federation
facility: Clinical Research Institute of Hematology and Transfusiology
city: Syktyvkar
country: Russian Federation
facility: Oncology Dispensary of Komi Republic
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Girona
country: Spain
facility: Hosp. Univ. Dr. Josep Trueta
city: Granada
country: Spain
facility: Hosp. Univ. Virgen de Las Nieves
city: La Laguna
country: Spain
facility: Hosp. Univ. de Canarias
city: Leon
country: Spain
facility: Hosp. de Leon
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. Infanta Leonor
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Pozuelo de Alarcon
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Valencia
country: Spain
facility: Hosp. Univ. Dr. Peset
city: Falun
country: Sweden
facility: Falu Lasarett
city: Helsingborg
country: Sweden
facility: Helsingborgs lasarett
city: Huddinge
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Lund
country: Sweden
facility: Skanes universitetssjukhus
city: Umea
country: Sweden
facility: Norrlands University Hospital
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Changhua
country: Taiwan
facility: Chang-Hua Christian Hospital
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Cherkasy
country: Ukraine
facility: Communal Nonprofit Enterprise 'Cherkasy Regional Oncology Dispensary Of Cherkasy Regional Council'
city: Dnepropetrovsk
country: Ukraine
facility: Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: SI Grigoriev Institute for Medical Radiology National Academy of Medical Science of Ukraine
city: Kiev
country: Ukraine
facility: National Cancer Institute, Dept. of chemotherapy of hemoblastosis
city: Kiev
country: Ukraine
facility: Kiev Marrow Transplantation Center, Bone Marrow Transplantation Department
city: Kiev
country: Ukraine
facility: State Institution 'National Scientific Center for Radiation Medicine of NAMS of Ukraine'
city: Lviv
country: Ukraine
facility: Institute of Blood Pathology and Transfusion Medicine of AMS of Ukraine
city: Mykolaiv
country: Ukraine
facility: Mykolaiv Regional Clinical Hospital
city: Poltava
country: Ukraine
facility: Ukrainian Medical Stomatological Academy, Poltava Regional Clinical Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary - Haematology
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: Guys St Thomas Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Surrey
country: United Kingdom
facility: Royal Marsden Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Usmani 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.
citation: Iida 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.
citation: Usmani 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.
citation: Mateos 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.