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A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens

Primary Purpose

Multiple Myeloma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Daratumumab
Bortezomib
Lenalidomide
Dexamethasone
Melphalan
Prednisone
Carfilzomib
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:

  • Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria

  • Measurable, secretory disease as defined by any of the following:

    1. Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL); or
    2. Urine M-protein level >= 200 milligram per 24 hours (mg/24 hours); or
    3. Light chain multiple myeloma (MM), for participants without measurable disease in the serum or urine: serum Immunoglobulin (Ig) free light chain (FLC) >= 10 mg/dL and abnormal FLC ratio

  • Meets one of the sets of the following criteria:

    1. For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP) regimen: newly diagnosed myeloma
    2. For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab + Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease
    3. D-Kd cohort: Participants must have received only 1 prior line of therapy for MM which included at least 2 consecutive cycles of lenalidomide therapy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2
  • During the study, during dose interruptions, and for 3 months after receiving the last dose of any component of the study treatment, a female participant must agree not to donate eggs (ova, oocytes) and male participants of reproductive potential must not donate semen or sperm during the study, during dose interruptions, or for 3 months after the last dose of any study drug

Exclusion Criteria:

  • History of malignancy (other than MM) unless all treatment of that malignancy was completed at least 2 years before consent and the participant 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
  • Exhibits clinical signs of meningeal involvement of MM
  • Either of the following: a) Chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) is less than (<) 50 percentage (%) of predicted normal b) Moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification c) For D-Kd cohort: Known infiltrative pulmonary disease or known pulmonary hypertension
  • Any of the following: a) Known to be seropositive for human immunodeficiency virus; b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (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) DNA levels. Those who are polymerase chain reaction (PCR) positive will be excluded
  • Known to be seropositive for hepatitis C (Anti-HCV antibody positive or HCV-RNA quantitation positive) except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy
  • For D-Kd cohort only: Transthoracic echocardiogram showing left ventricular ejection fraction (LVEF) <40%; uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic >99 mmHg despite optimal treatment

Sites / Locations

  • Cancer Center of Central Connecticut - Southington
  • Mayo Clinic in Florida
  • UF Health Cancer Center at Orlando Health
  • Karmonos Cancer Institute
  • Providence Cancer Center
  • Billings Clinic
  • Nebraska Hematology and Oncology
  • Southeast Nebraska Cancer Center
  • Nebraska Cancer Specialists
  • San Juan Oncology Associates
  • NYU Winthrop
  • Mt. Sinai School of Medicine
  • Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
  • Avera Medical Group - Oncology & Hematology
  • Utah Cancer Specialists
  • University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic
  • Liga Norte Riograndense Contra O Cancer
  • Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo
  • Ministerio da Saude - Instituto Nacional do Cancer
  • SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
  • Instituto de Assistencia Medica ao Servidor Publico Estadual - IAMSPE
  • Clinica Sao Germano
  • Fakultni nemocnice Brno
  • Fakultni nemocnice Hradec Kralove
  • Fakultni nemocnice Ostrava
  • Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
  • CHU de Nantes hôtel-Dieu
  • CHU de Bordeaux - Hospital Haut-Leveque
  • Centre hospitalier Lyon-Sud
  • CHU Bretonneau
  • CHU Nancy Brabois
  • Klinikum Chemnitz gGmbH
  • Universitaetsklinikum Hamburg Eppendorf
  • Asklepios Klinik Altona
  • Universitaetsklinikum Heidelberg
  • Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
  • Rambam Medical Center
  • Carmel Medical Center
  • Hadassah Medical Center
  • Galilee Medical Center
  • Sheba Medical Center
  • Tel-Aviv Sourasky Medical Center
  • Kanazawa University Hospital
  • Matsuyama Red Cross Hospital
  • Nagoya City University Hospital
  • Japanese Red Cross Medical Center
  • Inst. Cat. D'Oncologia-Badalona
  • Hosp. Clinic I Provincial de Barcelona
  • Inst. Cat. Doncologia-H Duran I Reynals
  • Hosp. Univ. Vall D Hebron
  • Hosp. Gral. Univ. Gregorio Maranon
  • Clinica Univ. de Navarra
  • Hosp. Univ. Ramon Y Cajal
  • Hosp. Univ. 12 de Octubre
  • Hosp. Son Llatzer
  • Clinica Univ. de Navarra
  • Hosp. Clinico Univ. de Salamanca
  • Hosp. Univ. Dr. Peset
  • Heart of England NHS Foundation Trust
  • Royal Bournemouth Hospital
  • Kent and Canterbury Hospital
  • Manchester Royal Infirmary
  • Derriford Hospital
  • Royal Stoke University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

Arm Description

Participants will receive daratumumab 1800 milligram (mg) by subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligram per square meter (mg/m^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.

Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1 then on Days 1 and 22 in Cycles 2 to 9 and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; bortezomib 1.3 mg/m^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m^2 orally on Days 1 to 4 of cycles 1 to 9.

Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or end of study.

Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days) then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; Carfilzomib 20 mg/m^2 intravenously (IV) on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or IV weekly for Cycles 1-9 then on Days 1, 8, 15 of each cycle for Cycles 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study.

Outcomes

Primary Outcome Measures

D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligrams (mg) per 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%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response
VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.

Secondary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of Daratumumab
Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days.
Percentage of Participants With Infusion-Related Reactions (IRRs)
Percentage of Participants with IRRs were reported. The administration-related systemic reactions are referred to as IRRs.
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response
VGPR or better rate was defined as the percentage of participants who achieved VGPR or CR (including sCR) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
D-VRd Cohort: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved a PR or better, IMWG criteria, during the study or during follow up. 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 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 PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Percentage of Participants With CR or Better Response
CR or better rate was defined as the percentage of participants with a CR or better response (that is, CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)
DOR was defined as the time from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death due to PD. PD is defined as an increase of 25% from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Percentage of Participants With Anti-Daratumumab Antibodies
Percentage of participants with antibodies to daratumumab were reported.
Percentage of Participants With Anti-rHuPH20 Antibodies
Percentage of participants with antibodies to rHuPH20 were reported.
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate
MRD negativity rate was defined as the percentage of participants who were considered MRD negative after MRD testing at any timepoint after the first dose by bone marrow aspirate. MRD negativity rate was assessed by next-generation sequencing at a threshold of <10^5.

Full Information

First Posted
January 22, 2018
Last Updated
September 12, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03412565
Brief Title
A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
Official Title
A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 26, 2018 (Actual)
Primary Completion Date
August 12, 2020 (Actual)
Study Completion Date
September 29, 2023 (Anticipated)

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
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the clinical benefit of subcutaneous (SC) daratumumab administered in combination with standard multiple myeloma (MM) regimens in participants with MM as measured by overall response rate (ORR) or very good partial response (VGPR) or better rate.
Detailed Description
The hypothesis is that the addition of daratumumab administered SC to standard MM regimens will improve responses compared to response data observed in completed phase 3 studies without daratumumab. Disease evaluations will include measurements of myeloma proteins, bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin. Safety will be measured by adverse events, laboratory test results, electrocardiogram (ECGs), vital sign measurements, physical examination findings, SC injection-site assessments, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status score. Study will consist of 3 phases (screening, treatment and follow-up) and duration of study is approximately 3 years.

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
Non-Randomized
Enrollment
265 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)
Arm Type
Experimental
Arm Description
Participants will receive daratumumab 1800 milligram (mg) by subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligram per square meter (mg/m^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.
Arm Title
D + Bortezomib + Melphalan + Prednisone (D-VMP)
Arm Type
Experimental
Arm Description
Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1 then on Days 1 and 22 in Cycles 2 to 9 and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; bortezomib 1.3 mg/m^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m^2 orally on Days 1 to 4 of cycles 1 to 9.
Arm Title
Daratumumab + Lenalidomide + Dexamethasone (D-Rd)
Arm Type
Experimental
Arm Description
Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or end of study.
Arm Title
Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm Type
Experimental
Arm Description
Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days) then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; Carfilzomib 20 mg/m^2 intravenously (IV) on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or IV weekly for Cycles 1-9 then on Days 1, 8, 15 of each cycle for Cycles 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study.
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Intervention Description
Daratumumab will be administered at a dose of 1800 mg by SC injection in Cycles 1 to 4 in D-VRd cohort and until documented progression of disease, unacceptable toxicity, or end of study for D-VMP, D-Rd and D-Kd cohorts.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
Bortezomib will be administered as 1.3 mg/m^2 SC injection in Cycles 1 to 4 in D-VRd cohort and in Cycles 1 to 9 in D-VMP cohort.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Lenalidomide will be administered as 25 mg capsule orally in Cycles 1 to 4 in D-VRd cohort and in all Cycles until documented progression of disease, unacceptable toxicity, or end of study in D-Rd cohort.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone will be administered as 20 mg orally or intravenously in Cycles 1 to 4 in D-VRd cohort; 40 mg orally or intravenously in all cycles and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Rd and D-Kd cohort.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Melphalan will be administered as 9 mg/m^2 orally in Cycles 1 to 9.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone will be administered as 60 mg/m^2 orally in cycles 1 to 9.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Intervention Description
Carfilzomib will be administered as 20 mg/m^2 IV on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Kd cohort.
Primary Outcome Measure Information:
Title
D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)
Description
ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligrams (mg) per 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%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Time Frame
Up to 2 years 3 months
Title
D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response
Description
VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
Time Frame
Up to 2 years and 3 months
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Description
Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days.
Time Frame
D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8
Title
Percentage of Participants With Infusion-Related Reactions (IRRs)
Description
Percentage of Participants with IRRs were reported. The administration-related systemic reactions are referred to as IRRs.
Time Frame
Up to 2 years and 3 months
Title
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response
Description
VGPR or better rate was defined as the percentage of participants who achieved VGPR or CR (including sCR) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
Time Frame
Up to 2 years and 3 months
Title
D-VRd Cohort: Overall Response Rate (ORR)
Description
ORR was defined as the percentage of participants who achieved a PR or better, IMWG criteria, during the study or during follow up. 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 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 PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Time Frame
Up to 2 years and 3 months
Title
Percentage of Participants With CR or Better Response
Description
CR or better rate was defined as the percentage of participants with a CR or better response (that is, CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
Time Frame
Up to 2 years and 3 months
Title
D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)
Description
DOR was defined as the time from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death due to PD. PD is defined as an increase of 25% from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time Frame
Up to 2 years and 3 months
Title
Percentage of Participants With Anti-Daratumumab Antibodies
Description
Percentage of participants with antibodies to daratumumab were reported.
Time Frame
Up to 10 months
Title
Percentage of Participants With Anti-rHuPH20 Antibodies
Description
Percentage of participants with antibodies to rHuPH20 were reported.
Time Frame
Up to 10 months
Title
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate
Description
MRD negativity rate was defined as the percentage of participants who were considered MRD negative after MRD testing at any timepoint after the first dose by bone marrow aspirate. MRD negativity rate was assessed by next-generation sequencing at a threshold of <10^5.
Time Frame
Up to 2 years and 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria Measurable, secretory disease as defined by any of the following: Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL); or Urine M-protein level >= 200 milligram per 24 hours (mg/24 hours); or Light chain multiple myeloma (MM), for participants without measurable disease in the serum or urine: serum Immunoglobulin (Ig) free light chain (FLC) >= 10 mg/dL and abnormal FLC ratio Meets one of the sets of the following criteria: For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP) regimen: newly diagnosed myeloma For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab + Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease D-Kd cohort: Participants must have received only 1 prior line of therapy for MM which included at least 2 consecutive cycles of lenalidomide therapy Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2 During the study, during dose interruptions, and for 3 months after receiving the last dose of any component of the study treatment, a female participant must agree not to donate eggs (ova, oocytes) and male participants of reproductive potential must not donate semen or sperm during the study, during dose interruptions, or for 3 months after the last dose of any study drug Exclusion Criteria: History of malignancy (other than MM) unless all treatment of that malignancy was completed at least 2 years before consent and the participant 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 Exhibits clinical signs of meningeal involvement of MM Either of the following: a) Chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) is less than (<) 50 percentage (%) of predicted normal b) Moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification c) For D-Kd cohort: Known infiltrative pulmonary disease or known pulmonary hypertension Any of the following: a) Known to be seropositive for human immunodeficiency virus; b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (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) DNA levels. Those who are polymerase chain reaction (PCR) positive will be excluded Known to be seropositive for hepatitis C (Anti-HCV antibody positive or HCV-RNA quantitation positive) except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy For D-Kd cohort only: Transthoracic echocardiogram showing left ventricular ejection fraction (LVEF) <40%; uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic >99 mmHg despite optimal treatment
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
Cancer Center of Central Connecticut - Southington
City
Southington
State/Province
Connecticut
ZIP/Postal Code
06489-3237
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
UF Health Cancer Center at Orlando Health
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Karmonos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Providence Cancer Center
City
Southfield
State/Province
Michigan
ZIP/Postal Code
48075
Country
United States
Facility Name
Billings Clinic
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Nebraska Hematology and Oncology
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68506
Country
United States
Facility Name
Southeast Nebraska Cancer Center
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68510
Country
United States
Facility Name
Nebraska Cancer Specialists
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
San Juan Oncology Associates
City
Farmington
State/Province
New Mexico
ZIP/Postal Code
87401
Country
United States
Facility Name
NYU Winthrop
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Mt. Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Avera Medical Group - Oncology & Hematology
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84121
Country
United States
Facility Name
University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Liga Norte Riograndense Contra O Cancer
City
Natal
ZIP/Postal Code
59062-000
Country
Brazil
Facility Name
Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo
City
Passo Fundo
ZIP/Postal Code
99010-090
Country
Brazil
Facility Name
Ministerio da Saude - Instituto Nacional do Cancer
City
Rio de Janeiro
ZIP/Postal Code
20230-130
Country
Brazil
Facility Name
SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
City
Sao Paulo
ZIP/Postal Code
04037-002
Country
Brazil
Facility Name
Instituto de Assistencia Medica ao Servidor Publico Estadual - IAMSPE
City
Sao Paulo
ZIP/Postal Code
04039-004
Country
Brazil
Facility Name
Clinica Sao Germano
City
São Paulo
ZIP/Postal Code
01455-010
Country
Brazil
Facility Name
Fakultni nemocnice Brno
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava
ZIP/Postal Code
70852
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
CHU de Nantes hôtel-Dieu
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
CHU de Bordeaux - Hospital Haut-Leveque
City
Pessac cedex
ZIP/Postal Code
33604
Country
France
Facility Name
Centre hospitalier Lyon-Sud
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Facility Name
CHU Bretonneau
City
Tours Cedex 9
ZIP/Postal Code
37044
Country
France
Facility Name
CHU Nancy Brabois
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Klinikum Chemnitz gGmbH
City
Chemnitz
ZIP/Postal Code
09113
Country
Germany
Facility Name
Universitaetsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Asklepios Klinik Altona
City
Hamburg
ZIP/Postal Code
22763
Country
Germany
Facility Name
Universitaetsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Carmel Medical Center
City
Haifa
ZIP/Postal Code
3436212
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Galilee Medical Center
City
Nahariya
ZIP/Postal Code
22100
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Tel-Aviv Sourasky Medical Center
City
Tel-Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Kanazawa University Hospital
City
Kanazawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Matsuyama Red Cross Hospital
City
Matsuyama
ZIP/Postal Code
790-8524
Country
Japan
Facility Name
Nagoya City University Hospital
City
Nagoya
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
Japanese Red Cross Medical Center
City
Shibuya
ZIP/Postal Code
150-8935
Country
Japan
Facility Name
Inst. Cat. D'Oncologia-Badalona
City
Badalona
ZIP/Postal Code
08916
Country
Spain
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. Univ. Vall D Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hosp. Gral. Univ. Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Clinica Univ. de Navarra
City
Madrid
ZIP/Postal Code
28027
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. Son Llatzer
City
Mallorca
ZIP/Postal Code
07198
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. Dr. Peset
City
Valencia
ZIP/Postal Code
46017
Country
Spain
Facility Name
Heart of England NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Kent and Canterbury Hospital
City
Canterbury
ZIP/Postal Code
CT1 3NG
Country
United Kingdom
Facility Name
Manchester Royal Infirmary
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Royal Stoke University Hospital
City
Stoke on Trent
ZIP/Postal Code
ST4 6QG
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens

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