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Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab

Primary Purpose

Multiple Myeloma

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Carfilzomib 20 mg/m^2
Carfilzomib 70 mg/m^2
Dexamethasone 40 mg
Dara-SC 1800 mg
Dexamethasone 20 mg
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Active Comparator

Experimental

Arm Label

Arm A: Carfilzomib+Dexamethasone (Kd)

Arm B: Dara-SC in combination with Kd (DKd)

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response
Percentage of participants achieving VGPR or better response according IMWG criteria for VGPR will be reported. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (<) 100 milligram (mg)/24 hours.

Secondary Outcome Measures

Overall Response Rate (ORR)
ORR is defined as percentage of participants who achieve partial response (PR) or better (including VGPR, CR, sCR) responses prior to subsequent anti-myeloma therapy. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours; If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%; additionally, if present at baseline, a >=50% reduction in the size of soft tissue PCs is also required.
Percentage of Participants Achieving Complete Response (CR) or Stringent Complete Response (sCR)
Complete response is based on serum M-Protein assessments. IMWG criteria for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and <5% PCs in bone marrow. IMWG criteria for sCR defined as, CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.
Progression Free Survival (PFS)
PFS is time from date of randomization to date of documented progressive disease (PD) on first line treatment given for multiple myeloma (MM) or death, whichever comes first. IMWG criteria for PD: >=25% from lowest response level in serum M-component (the absolute increase must be >=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the absolute increase must be >=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be >10 mg/dL. BMPC%: the absolute % must be >=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.
Overall Survival (OS)
OS is defined as the time from the date of first dose of study drug to date of death due to any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Percentage of participants who have achieved MRD negative status will be assessed.
Time to Next Treatment
Time to next treatment is defined as the time from randomization to the start of the next-line treatment.
Serum Concentrations of Daratumumab
Serum concentrations of daratumumab will be assessed.
Number of Participants with Anti-Daratumumab Antibodies
Number of participants who test positive for anti-daratumumab antibodies will be reported.
Number of Participants with Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies
Number of participants who test positive for anti-rHuPH20 antibodies will be reported.

Full Information

First Posted
March 11, 2019
Last Updated
March 6, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03871829
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
The decision was made to discontinue the 54767414MMY2065 study as the Data Review Committee recommendation was early stop of the study for futility.
Study Start Date
May 31, 2019 (Actual)
Primary Completion Date
October 24, 2022 (Actual)
Study Completion Date
January 10, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
88 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Carfilzomib+Dexamethasone (Kd)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm B: Dara-SC in combination with Kd (DKd)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib 20 mg/m^2
Intervention Description
Carfilzomib 20 mg/m^2 will be administered intravenously (IV).
Intervention Type
Drug
Intervention Name(s)
Carfilzomib 70 mg/m^2
Intervention Description
Carfilzomib 70 mg/m^2 will be administered IV.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone 40 mg
Intervention Description
Dexamethasone 40 mg will be administered as IV infusion or orally.
Intervention Type
Drug
Intervention Name(s)
Dara-SC 1800 mg
Intervention Description
Dara-SC 1800 mg will be administered by SC injection.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone 20 mg
Intervention Description
Dexamethasone 20 mg will be administered as IV infusion or orally.
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response
Description
Percentage of participants achieving VGPR or better response according IMWG criteria for VGPR will be reported. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (<) 100 milligram (mg)/24 hours.
Time Frame
Up to 6 years and 9 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is defined as percentage of participants who achieve partial response (PR) or better (including VGPR, CR, sCR) responses prior to subsequent anti-myeloma therapy. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours; If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%; additionally, if present at baseline, a >=50% reduction in the size of soft tissue PCs is also required.
Time Frame
Up to 6 years and 9 months
Title
Percentage of Participants Achieving Complete Response (CR) or Stringent Complete Response (sCR)
Description
Complete response is based on serum M-Protein assessments. IMWG criteria for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and <5% PCs in bone marrow. IMWG criteria for sCR defined as, CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.
Time Frame
Up to 6 years and 9 months
Title
Progression Free Survival (PFS)
Description
PFS is time from date of randomization to date of documented progressive disease (PD) on first line treatment given for multiple myeloma (MM) or death, whichever comes first. IMWG criteria for PD: >=25% from lowest response level in serum M-component (the absolute increase must be >=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the absolute increase must be >=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be >10 mg/dL. BMPC%: the absolute % must be >=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.
Time Frame
Up to 6 years and 9 months
Title
Overall Survival (OS)
Description
OS is defined as the time from the date of first dose of study drug to date of death due to any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.
Time Frame
Up to 6 years and 9 months
Title
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Description
Percentage of participants who have achieved MRD negative status will be assessed.
Time Frame
Up to 6 years and 9 months
Title
Time to Next Treatment
Description
Time to next treatment is defined as the time from randomization to the start of the next-line treatment.
Time Frame
Up to 6 years and 9 months
Title
Serum Concentrations of Daratumumab
Description
Serum concentrations of daratumumab will be assessed.
Time Frame
Arm A: Cycle 1 (each cycle of 28 days) Day 1 (Cycle 1 Day 1), Cycle 3 Day 1; Arm B: Cycle 1 Day1, Cycle 3 Day 1, Cycle 7 Day 1 and Follow Up (post treatment Week 8)
Title
Number of Participants with Anti-Daratumumab Antibodies
Description
Number of participants who test positive for anti-daratumumab antibodies will be reported.
Time Frame
Arm A: Cycle 1 (each cycle of 28 days) Day 1 (Cycle 1 Day 1), Cycle 3 Day 1; Arm B: Cycle 1 Day1, Cycle 3 Day 1, Cycle 7 Day 1 and Follow Up (post treatment Week 8)
Title
Number of Participants with Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies
Description
Number of participants who test positive for anti-rHuPH20 antibodies will be reported.
Time Frame
Arm A: Cycle 1 (each cycle of 28 days) Day 1 (Cycle 1 Day 1), Cycle 3 Day 1; Arm B: Cycle 1 Day1, Cycle 3 Day 1, Cycle 7 Day 1 and Follow Up (post treatment Week 8)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Oncology Institute of Hope and Innovation
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85745
Country
United States
Facility Name
American Institute of Research (AIR)
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Fort Wayne Medical Oncology and Hematology, Inc.
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
Karmanos Cancer Institute - Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1032
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Cleveland Clinic Main Campus
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Baylor Scott and White Health
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Millennium Oncology
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
ZNA Stuivenberg
City
Antwerpen
ZIP/Postal Code
2060
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Universidade Estadual De Campinas
City
Campinas
ZIP/Postal Code
13083-878
Country
Brazil
Facility Name
Liga Paranaense de Combate ao Cancer
City
Curitiba
ZIP/Postal Code
81520-060
Country
Brazil
Facility Name
Universidade Federal de Goias - Hospital das Clinicas da UFG
City
Goiânia
ZIP/Postal Code
74605-020
Country
Brazil
Facility Name
Liga Norte Riograndense Contra O Cancer
City
Natal
ZIP/Postal Code
59062-000
Country
Brazil
Facility Name
Irmandade Santa Casa de Misericordia de Porto Alegre
City
Porto Alegre
ZIP/Postal Code
90050-170
Country
Brazil
Facility Name
Ministerio da Saude - Instituto Nacional do Cancer
City
Rio de Janeiro
ZIP/Postal Code
20230-130
Country
Brazil
Facility Name
Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
City
Rio de Janeiro
ZIP/Postal Code
22775-001
Country
Brazil
Facility Name
Hospital Sao Rafael
City
Salvador
ZIP/Postal Code
41253-190
Country
Brazil
Facility Name
CEHON
City
Salvador
ZIP/Postal Code
45995-000
Country
Brazil
Facility Name
Instituto de Ensino e Pesquisa São Lucas
City
Sao Paulo
ZIP/Postal Code
01236-030
Country
Brazil
Facility Name
Fundação Antônio Prudente - A.C. Camargo Cancer Center
City
Sao Paulo
ZIP/Postal Code
01509900
Country
Brazil
Facility Name
Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
City
Sao Paulo
ZIP/Postal Code
03102-002
Country
Brazil
Facility Name
Real e Benemérita Associação Portuguesa de Beneficência
City
São Paulo
ZIP/Postal Code
01321-001
Country
Brazil
Facility Name
Clinica Sao Germano
City
São Paulo
ZIP/Postal Code
01455-010
Country
Brazil
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Aarhus University Hospital
City
Aarhus N
ZIP/Postal Code
DK-8200
Country
Denmark
Facility Name
Regionshospitalet i Holstebro
City
Holstebro
ZIP/Postal Code
7500
Country
Denmark
Facility Name
Haematological Research unit HFE-X OUH.
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Vejle Hospital
City
Vejle
ZIP/Postal Code
DK-7100
Country
Denmark
Facility Name
Hopital Claude Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU de Montpellier, Hopital Saint-Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Centre Hospitalier Emile Muller
City
Mulhouse
ZIP/Postal Code
68100
Country
France
Facility Name
Hotel Dieu
City
Nantes
ZIP/Postal Code
44035
Country
France
Facility Name
Hopitaux Universitaires Est Parisien Hopital Saint Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Hopital de la Pitie Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hôpital Necker-Enfants Malades
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Fentre F Magendie, Hôpital Haut Leveque, CHU Bordeaux
City
Pessac
ZIP/Postal Code
33600
Country
France
Facility Name
Centre Hospitalier Lyon-Sud Service d'hematologie
City
Pierre Benite
ZIP/Postal Code
69310
Country
France
Facility Name
CHU Poitiers - Hôpital la Milétrie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Chu Rennes - Hopital Pontchaillou
City
Rennes Cedex
ZIP/Postal Code
35033
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31052
Country
France
Facility Name
CHU Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
CHU Nancy Brabois
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Universitätsklinik Carl Gustav Carus, Med. Klinik u. Poliklinik I
City
Dresden
ZIP/Postal Code
1307
Country
Germany
Facility Name
Evangelisches Krankenhaus Essen-Werden
City
Essen
ZIP/Postal Code
45239
Country
Germany
Facility Name
Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
D-45147
Country
Germany
Facility Name
Universitätsklinik Hamburg-Eppendorf UKE
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
St. Barbara-Klinik Hamm GmbH
City
Hamm
ZIP/Postal Code
59075
Country
Germany
Facility Name
Praxisklinik für Haematologie und Onkologie Koblenz
City
Koblenz
ZIP/Postal Code
56068
Country
Germany
Facility Name
Universitaetsklinikum Koeln
City
Koeln
ZIP/Postal Code
50397
Country
Germany
Facility Name
Universitätsmedizin der Johannes gutenberg-Universität; III. Med. Klinik - Germany
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Onkologische Schwerpunkt Praxis
City
Saarbrucken
Country
Germany
Facility Name
Klinikum der Eberhard-Karls-Universität/Abt. für innere Med. II/Hämatologie/Onkologie-Germany
City
Tubingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Schwarzwald-Baar Klinikum
City
Villingen-Schwenningen
ZIP/Postal Code
78052
Country
Germany
Facility Name
Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Alexandra General Hospital of Athens
City
Athens Attica
ZIP/Postal Code
115 28
Country
Greece
Facility Name
University of Athens - Evaggelismos Hospital (Evangelismos Hospital)
City
Athens
ZIP/Postal Code
106 76
Country
Greece
Facility Name
University Hospital Of Larissa
City
Larisa
ZIP/Postal Code
41110
Country
Greece
Facility Name
University General Hospital of Rio
City
Patra
ZIP/Postal Code
26500
Country
Greece
Facility Name
Anticancer Hospital of Thessaloniki 'Theageneio'
City
Thessaloniki
ZIP/Postal Code
546 39
Country
Greece
Facility Name
Azienda Ospedaliera Papa Giovanni XXIII
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
Facility Name
Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Careggi
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
IRCCS Azienda Ospedaliera San Martino - IST
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
San Martino Hospital
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Asst Ovest Milanese - Ospedale Di Legnano
City
Legnano
ZIP/Postal Code
20025
Country
Italy
Facility Name
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
City
Meldola
ZIP/Postal Code
47014
Country
Italy
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Ospedale Maggiore della Carità
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Casa di Cura La Maddalena
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Ospedale Villa Sofia-Cervello
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Universita Degli Studi di Roma 'Tor Vergata'
City
Roma
ZIP/Postal Code
00133
Country
Italy
Facility Name
Sapienza University of Rome
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
ASL ROMA
City
Roma
ZIP/Postal Code
30 - 00153
Country
Italy
Facility Name
Fondazione Policlinico Universitario A. Gemelli IRCCS
City
Rome
ZIP/Postal Code
00168
Country
Italy
Facility Name
IRCCS Ospedale Casa Sollievo della Sofferenza
City
San Giovanni Rotondo
ZIP/Postal Code
71013
Country
Italy
Facility Name
Azienda Ospedaliera Santa Maria
City
Terni
ZIP/Postal Code
5100
Country
Italy
Facility Name
Albert Schweitzer ziekenhuis-lokatie Dordwijk
City
Dordrecht
ZIP/Postal Code
3318 AT
Country
Netherlands
Facility Name
Zuyderland Medical Center
City
Sittard
ZIP/Postal Code
6130 MB
Country
Netherlands
Facility Name
Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Szpital Wojewodzki w Opolu
City
Opole
ZIP/Postal Code
45-061
Country
Poland
Facility Name
Szpital Magodent
City
Warszawa
ZIP/Postal Code
01-748
Country
Poland
Facility Name
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
City
Wroclaw
ZIP/Postal Code
50-367
Country
Poland
Facility Name
Emergency Hospital of Dzerzhinsk
City
Dzerzhinsk
ZIP/Postal Code
606019
Country
Russian Federation
Facility Name
S.P. Botkin Moscow City Clinical Hospital
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
Nizhniy Novgorod Region Clinical Hospital
City
Nizhny Novgorod
ZIP/Postal Code
603126
Country
Russian Federation
Facility Name
Ryazan Regional Clinical Hospital
City
Ryazan
ZIP/Postal Code
390003
Country
Russian Federation
Facility Name
Oncological dispensary #2
City
Sochi
ZIP/Postal Code
354057
Country
Russian Federation
Facility Name
Clinical Research Institute of Hematology and Transfusiology
City
St-Petersburg
ZIP/Postal Code
191024
Country
Russian Federation
Facility Name
Oncology Dispensary of Komi Republic
City
Syktyvkar
ZIP/Postal Code
167904
Country
Russian Federation
Facility Name
Hosp. Clinic I Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Inst. Cat. Doncologia-H Duran I Reynals
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hosp. de Jerez de La Frontera
City
Jerez de la Frontera
ZIP/Postal Code
11407
Country
Spain
Facility Name
Hosp. de Leon
City
Leon
ZIP/Postal Code
24080
Country
Spain
Facility Name
Hosp. Univ. Ramon Y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hosp. Univ. 12 De Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hosp. Univ. de La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hosp. Costa Del Sol
City
Malaga
ZIP/Postal Code
29603
Country
Spain
Facility Name
Hosp. Univ. Son Espases
City
Palma
ZIP/Postal Code
7120
Country
Spain
Facility Name
Clinica Univ. De Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hosp. Clinico Univ. de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hosp. Univ. de Canarias
City
San Cristóbal de La Laguna
ZIP/Postal Code
38320
Country
Spain
Facility Name
Hosp. Virgen Del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hosp. Gral. Univ. de Toledo
City
Toledo
ZIP/Postal Code
45007
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab

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