Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to daratumumab-containing therapy with response duration of at least 4 months
- Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or >60 days after cessation of treatment
- Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and completed daratumumab at least 3 months prior to randomization. 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 per day [mg/day] for 4 days) would not be considered prior lines of therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
- Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization
Exclusion Criteria:
- Previous treatment with daratumumab within the last 3 months prior to randomization
- Discontinuation of daratumumab due to a daratumumab-related adverse event (AE)
- 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
- Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
- Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV) with one or more of the following: not receiving highly active antiretroviral therapy (ART), had a change in ART within 6 months of the start of screening, receiving ART that may interfere with study treatment, cluster of differentiation (CD)4 count <350 (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening, and not agreeing to start ART and be on ART >4 weeks plus having HIV viral load <400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (example: participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
Sites / Locations
- Banner MD Anderson Cancer Center
- Oncology Institute of Hope and Innovation
- American Institute of Research (AIR)
- Fort Wayne Medical Oncology and Hematology, Inc.
- Karmanos Cancer Institute - Wayne State University
- Mayo Clinic - Rochester
- Washington University School of Medicine
- Weill Medical College of Cornell University
- Cleveland Clinic Main Campus
- Baylor Scott and White Health
- Millennium Oncology
- ZNA Stuivenberg
- UZ Gent
- Universidade Estadual De Campinas
- Liga Paranaense de Combate ao Cancer
- Universidade Federal de Goias - Hospital das Clinicas da UFG
- Liga Norte Riograndense Contra O Cancer
- Irmandade Santa Casa de Misericordia de Porto Alegre
- Ministerio da Saude - Instituto Nacional do Cancer
- Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
- Hospital Sao Rafael
- CEHON
- Instituto de Ensino e Pesquisa São Lucas
- Fundação Antônio Prudente - A.C. Camargo Cancer Center
- Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
- Real e Benemérita Associação Portuguesa de Beneficência
- Clinica Sao Germano
- Tom Baker Cancer Centre
- Aarhus University Hospital
- Regionshospitalet i Holstebro
- Haematological Research unit HFE-X OUH.
- Vejle Hospital
- Hopital Claude Huriez
- CHU de Montpellier, Hopital Saint-Eloi
- Centre Hospitalier Emile Muller
- Hotel Dieu
- Hopitaux Universitaires Est Parisien Hopital Saint Antoine
- Hopital de la Pitie Salpetriere
- Hôpital Necker-Enfants Malades
- Fentre F Magendie, Hôpital Haut Leveque, CHU Bordeaux
- Centre Hospitalier Lyon-Sud Service d'hematologie
- CHU Poitiers - Hôpital la Milétrie
- Chu Rennes - Hopital Pontchaillou
- Institut Claudius Regaud
- CHU Bretonneau
- CHU Nancy Brabois
- Universitätsklinik Carl Gustav Carus, Med. Klinik u. Poliklinik I
- Evangelisches Krankenhaus Essen-Werden
- Universitatsklinikum Essen
- Universitätsklinik Hamburg-Eppendorf UKE
- St. Barbara-Klinik Hamm GmbH
- Praxisklinik für Haematologie und Onkologie Koblenz
- Universitaetsklinikum Koeln
- Universitätsmedizin der Johannes gutenberg-Universität; III. Med. Klinik - Germany
- Onkologische Schwerpunkt Praxis
- Klinikum der Eberhard-Karls-Universität/Abt. für innere Med. II/Hämatologie/Onkologie-Germany
- Schwarzwald-Baar Klinikum
- Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii
- Alexandra General Hospital of Athens
- University of Athens - Evaggelismos Hospital (Evangelismos Hospital)
- University Hospital Of Larissa
- University General Hospital of Rio
- Anticancer Hospital of Thessaloniki 'Theageneio'
- Azienda Ospedaliera Papa Giovanni XXIII
- Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi
- Azienda Ospedaliera Universitaria Careggi
- IRCCS Azienda Ospedaliera San Martino - IST
- San Martino Hospital
- Asst Ovest Milanese - Ospedale Di Legnano
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
- ASST Grande Ospedale Metropolitano Niguarda
- Ospedale Maggiore della Carità
- Casa di Cura La Maddalena
- Ospedale Villa Sofia-Cervello
- Fondazione IRCCS Policlinico San Matteo
- Universita Degli Studi di Roma 'Tor Vergata'
- Sapienza University of Rome
- ASL ROMA
- Fondazione Policlinico Universitario A. Gemelli IRCCS
- IRCCS Ospedale Casa Sollievo della Sofferenza
- Azienda Ospedaliera Santa Maria
- Albert Schweitzer ziekenhuis-lokatie Dordwijk
- Zuyderland Medical Center
- Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
- Szpital Wojewodzki w Opolu
- Szpital Magodent
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
- Emergency Hospital of Dzerzhinsk
- S.P. Botkin Moscow City Clinical Hospital
- Nizhniy Novgorod Region Clinical Hospital
- Ryazan Regional Clinical Hospital
- Oncological dispensary #2
- Clinical Research Institute of Hematology and Transfusiology
- Oncology Dispensary of Komi Republic
- Hosp. Clinic I Provincial de Barcelona
- Inst. Cat. Doncologia-H Duran I Reynals
- Hosp. de Jerez de La Frontera
- Hosp. de Leon
- Hosp. Univ. Ramon Y Cajal
- Hosp. Univ. 12 De Octubre
- Hosp. Univ. de La Paz
- Hosp. Costa Del Sol
- Hosp. Univ. Son Espases
- Clinica Univ. De Navarra
- Hosp. Clinico Univ. de Salamanca
- Hosp. Univ. de Canarias
- Hosp. Virgen Del Rocio
- Hosp. Gral. Univ. de Toledo
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm A: Carfilzomib+Dexamethasone (Kd)
Arm B: Dara-SC in combination with Kd (DKd)
Participants will receive carfilzomib 20 milligram per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.
Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.