Clinical trial NCT03871829: Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab
Official title: A Phase 2 Study of Daratumumab Subcutaneous (Dara-SC) Administration in Combination With Carfilzomib and Dexamethasone (DKd) Compared With Carfilzomib and Dexamethasone (Kd) in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab to Evaluate Daratumumab Retreatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-03-12
Enrollment: 88
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 compare the efficacy (rate of very good partial response \[VGPR\] or better as best response as defined by the International Myeloma Working Group \[IMWG\] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.

Detailed description: For relapsed or refractory multiple myeloma, the treatment is determined on an individual basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often retreated with drugs that have same mechanism of action to which they have been sensitive. The disease becomes refractory and all effective treatment options are exhausted. Daratumumab is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in adult participants with relapsed refractory MM who had 1 to 3 prior line(s) of treatment including a line containing daratumumab to evaluate daratumumab retreatment. The MM treatment is determined on an individual basis where patient's age, prior therapy, bone marrow function, co-morbidities, patient preference and time to relapse are considered. Common standard of care regimens use either PI or an IMiD in combination with dexamethasone with or without a mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a transmembrane glycoprotein, in a variety of hematological malignancies including multiple myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be performed during Screening phase. During the Treatment Phase, participants will be randomized to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed. Follow-up will continue until the end of study.

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)

Primary outcomes:
measure: Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response
timeFrame: Up to 3 years and 4 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years and 7 months
measure: Percentage of Participants Achieving Complete Response (CR) or Better
timeFrame: Up to 3 years and 7 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 3 years and 7 months
measure: Overall Survival (OS)
timeFrame: Up to 3 years and 7 months
measure: Percentage of Participants With Negative Minimal Residual Disease (MRD)
timeFrame: Up to 3 years and 7 months
measure: Time to Next Treatment
timeFrame: Up to 3 years and 7 months
measure: Serum Concentrations of Daratumumab
timeFrame: Day 1 of Cycles 1, 3, and 7 (each cycle of 28 days) and Follow Up (post treatment Week 8; up to 30.3 months)
measure: Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies
timeFrame: Up to end of study; up to 30.3 months
measure: Number of Participants With Anti-Daratumumab Antibodies
timeFrame: Up to end of study; up to 30.3 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Oncology Institute of Hope and Innovation
state: Arizona
city: Whittier
country: United States
facility: American Institute of Research (AIR)
state: California
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
city: Detroit
country: United States
facility: Karmanos Cancer Institute - Wayne State University
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Dallas
country: United States
facility: Baylor Scott and White Health
state: Texas
city: Houston
country: United States
facility: Millennium Oncology
state: Texas
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Gent
country: Belgium
facility: UZ Gent
city: Campinas
country: Brazil
facility: Universidade Estadual De Campinas
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate ao Cancer
city: Goiania
country: Brazil
facility: Universidade Federal de Goias - Hospital das Clinicas da UFG
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Ministerio da Saude Instituto Nacional do Cancer
city: Rio de Janeiro
country: Brazil
facility: Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
city: Salvador
country: Brazil
facility: CEHON
city: Sao Paulo
country: Brazil
facility: Instituto de Ensino e Pesquisa São Lucas
city: Sao Paulo
country: Brazil
facility: Fundacao Antonio Prudente A C Camargo Cancer Center
city: Sao Paulo
country: Brazil
facility: Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
city: São Paulo
country: Brazil
facility: Real e Benemerita Associacao Portuguesa de Beneficencia
city: São Paulo
country: Brazil
facility: Clinica Sao Germano
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Holstebro
country: Denmark
facility: Regionshospitalet i Holstebro
city: Odense
country: Denmark
facility: Haematological Research unit HFE-X OUH.
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Lille
country: France
facility: Hopital Claude Huriez
city: Montpellier
country: France
facility: CHU de Montpellier Hopital Saint Eloi
city: Mulhouse
country: France
facility: Centre Hospitalier Emile Muller
city: Nantes
country: France
facility: Hotel Dieu
city: Paris
country: France
facility: Hopitaux Universitaires Est Parisien Hopital Saint Antoine
city: Paris
country: France
facility: Hopital de la Pitie Salpetriere
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Pessac
country: France
facility: Fentre F Magendie, Hôpital Haut Leveque, CHU Bordeaux
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon-Sud Service d'hematologie
city: Poitiers
country: France
facility: CHU Poitiers - Hopital la Miletrie
city: Rennes Cedex
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: CHU Bretonneau
city: Vandoeuvre Les Nancy
country: France
facility: CHU Nancy Brabois
city: Dresden
country: Germany
facility: Universitätsklinik Carl Gustav Carus, Med. Klinik u. Poliklinik I
city: Essen
country: Germany
facility: Evangelisches Krankenhaus Essen-Werden
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Hamburg
country: Germany
facility: Universitatsklinik Hamburg Eppendorf UKE
city: Hamm
country: Germany
facility: St. Barbara-Klinik Hamm GmbH
city: Koblenz
country: Germany
facility: Praxisklinik für Haematologie und Onkologie Koblenz
city: Koeln
country: Germany
facility: Universitaetsklinikum Koelnt
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes gutenberg-Universität; III. Med. Klinik - Germany
city: Saarbrucken
country: Germany
facility: Onkologische Schwerpunkt Praxis
city: Tubingen
country: Germany
facility: Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii
city: Athens Attica
country: Greece
facility: Alexandra General Hospital of Athens
city: Athens
country: Greece
facility: University of Athens - Evaggelismos Hospital (Evangelismos Hospital)
city: Larisa
country: Greece
facility: University Hospital Of Larissa
city: Patra
country: Greece
facility: University General Hospital of Rio
city: Thessaloniki
country: Greece
facility: Anticancer Hospital of Thessaloniki Theageneio
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Genova
country: Italy
facility: IRCCS Azienda Ospedaliera San Martino - IST
city: Genova
country: Italy
facility: San Martino Hospital
city: Legnano
country: Italy
facility: Asst Ovest Milanese - Ospedale Di Legnano
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Novara
country: Italy
facility: Ospedale Maggiore della Carita
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena
city: Palermo
country: Italy
facility: Ospedale Villa Sofia-Cervello
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Universita Degli Studi di Roma Tor Vergata
city: Roma
country: Italy
facility: Sapienza University of Rome
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli IRCCS
city: Roma
country: Italy
facility: ASL ROMA
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis-lokatie Dordwijk
city: Sittard
country: Netherlands
facility: Zuyderland Medical Center
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu
city: Warszawa
country: Poland
facility: Szpital Magodent
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
city: Dzerzhinsk
country: Russian Federation
facility: Emergency Hospital of Dzerzhinsk
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Clinical Hospital
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Hospital
city: Sochi
country: Russian Federation
facility: Oncological dispensary #2
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: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Jerez de la Frontera
country: Spain
facility: Hosp. de Jerez de La Frontera
city: Leon
country: Spain
facility: Hosp. de Leon
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. de La Paz
city: Malaga
country: Spain
facility: Hosp. Costa Del Sol
city: Palma
country: Spain
facility: Hosp. Univ. Son Espases
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: San Cristóbal de La Laguna
country: Spain
facility: Hosp. Univ. de Canarias
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Toledo
country: Spain
facility: Hosp. Gral. Univ. de Toledo
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: