Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the efficacy of daratumumab in combination with lenalidomide and dexamethasone to that of lenalidomide and dexamethasone in terms of progression-free survival (PFS) in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital or medical school team work on a medical research study) study in participants with newly diagnosed multiple myeloma and who are not candidates for high dose chemotherapy and ASCT. All the eligible participants will be randomly assigned to receive either lenalidomide and dexamethasone (Rd) (Arm A) or daratumumab in combination with lenalidomide and dexamethasone (DRd) (Arm B). Daratumumab (16 milligram per kilogram [mg/kg]) will be administered weekly for first 8 weeks (Cycles 1 to 2) of treatment and then every other week for 16 weeks (Cycles 3 to 6), then every 4 weeks (from Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide will be administered at a dose of 25 mg orally on Days 1 through 21 of each 28-day cycle, and dexamethasone will be administered at a dose of 40 mg once a week for both treatment arms. Participants in both treatment arms will continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity. All participants randomized to Treatment Arm B (DRd) in this study initially received daratumumab IV formulation; however, following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Participants in Arm A who have sponsor-confirmed disease progression may have the option to receive daratumumab provided by the sponsor (in any subsequent line of therapy) in the Follow-up phase. The study consists of 3 phases: Screening Phase (within 21 days prior to the first dose administration on Day 1), Treatment Phase (Day 1 up to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, consent withdrawal, or study end, whichever occurs first). The maximum duration of study will be 7 years after last participant is randomized. Efficacy will primarily be evaluated by PFS. Participants' safety will be monitored throughout the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Lenalidomide and Dexamethasone (Rd) Participants will receive Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first. |
Drug: Daratumumab IV
Daratumumab will be administered at a dose of 16 milligram per kilogram (mg/kg) by intravenous (IV) infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks until documented progression of disease, unacceptable toxicity, or end of study (maximum up to 7 years).
Other Names:
Drug: Lenalidomide
Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.
Drug: Dexamethasone
Dexamethasone 40 mg orally or intravenously once in a week.
|
| Active Comparator: Daratumumab + Lenalidomide + Dexamethasone (DRd) Participants will receive Daratumumab 16 milligram per kilogram (mg/kg) by intravenous infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks, Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first. |
Drug: Lenalidomide
Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.
Drug: Dexamethasone
Dexamethasone 40 mg orally or intravenously once in a week.
Drug: Daratumumab SC
Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study end. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Primary: Progression-free Survival (PFS) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or clinical cut-off (CCO) whichever occurs first (up to 3.5 years)]
PFS is defined as time from date of randomization to either progressive disease (PD) or death, whichever occurs first based on computerized algorithm as per International Myeloma Working Group (IMWG) criteria. PD is defined as an increase of 25 percent (%) from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than [>]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 Plasma cell (PC) proliferative disorder.
Secondary Outcome Measures
- Percentage of Participants With Complete Response (CR) or Better [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
CR or better is defined as percentage of participants with a CR or better (CR or stringent complete response [sCR]) based on computerized algorithm as per IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. In participants with only measurable disease by serum FLC levels a normal serum FLC ratio is required. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
- Percentage of Participants With Very Good Partial Response (VGPR) or Better [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
VGPR or better is defined as the percentage of participants with a response of VGPR or better (VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. In participants with only measurable disease by serum FLC levels a >90% decrease in the difference between involved and uninvolved FLC levels is required.
- Percentage of Participants With Negative Minimal Residual Disease (MRD) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
MRD negativity rate is defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the date of randomization by evaluation of bone marrow aspirates. MRD was assessed in participants who achieved CR or better.
- Overall Response Rate (ORR) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
ORR is defined as the percentage of participants who achieved partial response (PR) or better (PR, VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. PR is defined as >=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. A >=50% reduction in the size of soft tissue plasmacytomas is also required.
- Overall Survival (OS) [From randomization to death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
OS was measured from the date of randomization to the date of the death.
- Time to Disease Progression (TTP) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
TTP is defined as the time from the date of randomization to the date of PD based on computerized algorithm as per IMWG criteria, or death due to PD.
- Time to Response [From randomization to first response (PR or better) (up to 7.8 years)]
Time to response is defined as the time from the date of randomization to the first efficacy evaluation that met criteria for PR or better based on computerized algorithm as per IMWG criteria. 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. A >=50% reduction in the size of soft tissue plasmacytomas is also required.
- Duration of Response (DoR) [From first response (PR of better) to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
DoR is defined as the time from the date of initial response (PR or better) to the date of PD, based on computerized algorithm as per IMWG criteria.
- Time to Subsequent Anti-myeloma Treatment [From randomization to start of first subsequent anti-myeloma treatment, death, withdrawal of consent to study participation or CCO whichever is first (up to 7.8 years)]
Time to subsequent anti-myeloma treatment is defined as the time from randomization to the start of first line of subsequent anti-myeloma treatment or death, whichever occurs first.
- Progression-free Survival on Next Line of Therapy (PFS2) [From randomization to disease progression on first line of subsequent anti-myeloma therapy, death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]
PFS2 is defined as the time from randomization to progression on the first line of subsequent anti-myeloma therapy or death, whichever occurs first. Disease progression on first line of subsequent anti-myeloma treatment was based on investigator judgment. Participants that were censored for PFS1 were also censored for PFS2.
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Global Health Status Score to Day 1 of Cycle 3, 6, 9 and 12 [Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)]
EORTC QLQ-C30 is 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.
- Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) to Day 1 of Cycle 3, 6, 9 and 12 [Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)]
EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
- Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score to Day 1 of Cycle 3, 6, 9 and 12 [Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)]
EQ-5D-5L is standardized, participant-reported questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5-dimension scores were combined and converted into single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of individual (but allows for values less than 0 by United kingdom [UK] scoring algorithm).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant must have documented multiple myeloma satisfying the CRAB (calcium elevation, renal insufficiency, anemia and bone abnormalities) criteria, monoclonal plasma cells in the bone marrow greater than or equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma and measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >=1.0 gram/deciliter [g/dL] or urine M-protein level >=200 milligram[mg]/24 hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >=0.5 g/dL or urine M-protein level >=200 mg/24 hrs); or (c) light chain multiple myeloma without measurable disease in serum or urine (serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
-
Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
-
Participants who are newly diagnosed and not considered for high-dose chemotherapy due to: being age >=65 years; or participants less than (<) 65 years with presence of important comorbid condition(s) likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. Sponsor review and approval of participants below 65 years of age is required before randomization
-
Women of childbearing potential must commit to either abstain continuously from sexual intercourse or to use 2 methods of reliable birth control simultaneously as deemed appropriate by the Investigator. Contraception must begin 4 weeks prior to dosing and must continue for 3 months after the last dose of daratumumab
-
Man, who is sexually active with a woman of child-bearing potential must agree to use a latex or synthetic condom, even if he had a successful vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator, and must also agree to not donate sperm during the study and for 4 weeks after last dose of lenalidomide and 4 months after last dose of daratumumab
Exclusion Criteria:
-
Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage)
-
Participant has a diagnosis of Waldenström's disease, or other conditions in which IgM M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
-
Participant has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)
-
Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment
-
Participant has had radiation therapy within 14 days of randomization
-
Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] <50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)
-
Participants with known or suspected COPD must have a FEV1 test during Screening
-
Participant is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-HCV antibody positive or HCV-ribonucleic acid [RNA] quantitation positive)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | ||
| 2 | Mobile | Alabama | United States | ||
| 3 | Glendale | Arizona | United States | ||
| 4 | Berkeley | California | United States | ||
| 5 | Beverly Hills | California | United States | ||
| 6 | El Cajon | California | United States | ||
| 7 | Greenbrae | California | United States | ||
| 8 | Los Angeles | California | United States | ||
| 9 | Oceanside | California | United States | ||
| 10 | San Diego | California | United States | ||
| 11 | West Hills | California | United States | ||
| 12 | Whittier | California | United States | ||
| 13 | Denver | Colorado | United States | ||
| 14 | Fort Collins | Colorado | United States | ||
| 15 | Glenwood Springs | Colorado | United States | ||
| 16 | New Haven | Connecticut | United States | ||
| 17 | Norwalk | Connecticut | United States | ||
| 18 | Washington | District of Columbia | United States | ||
| 19 | Boca Raton | Florida | United States | ||
| 20 | Boynton Beach | Florida | United States | ||
| 21 | Fort Lauderdale | Florida | United States | ||
| 22 | Fort Myers | Florida | United States | ||
| 23 | Hollywood | Florida | United States | ||
| 24 | Jacksonville | Florida | United States | ||
| 25 | Lake City | Florida | United States | ||
| 26 | Saint Petersburg | Florida | United States | ||
| 27 | Weston | Florida | United States | ||
| 28 | Atlanta | Georgia | United States | ||
| 29 | Augusta | Georgia | United States | ||
| 30 | Macon | Georgia | United States | ||
| 31 | Marietta | Georgia | United States | ||
| 32 | Chicago | Illinois | United States | ||
| 33 | Niles | Illinois | United States | ||
| 34 | Fort Wayne | Indiana | United States | ||
| 35 | Iowa City | Iowa | United States | ||
| 36 | Louisville | Kentucky | United States | ||
| 37 | Lafayette | Louisiana | United States | ||
| 38 | Marrero | Louisiana | United States | ||
| 39 | Shreveport | Louisiana | United States | ||
| 40 | Annapolis | Maryland | United States | ||
| 41 | Baltimore | Maryland | United States | ||
| 42 | Frederick | Maryland | United States | ||
| 43 | Boston | Massachusetts | United States | ||
| 44 | Detroit | Michigan | United States | ||
| 45 | Duluth | Minnesota | United States | ||
| 46 | Rochester | Minnesota | United States | ||
| 47 | Kansas City | Missouri | United States | ||
| 48 | Saint Louis | Missouri | United States | ||
| 49 | Omaha | Nebraska | United States | ||
| 50 | Hooksett | New Hampshire | United States | ||
| 51 | Brick | New Jersey | United States | ||
| 52 | Hackensack | New Jersey | United States | ||
| 53 | Livingston | New Jersey | United States | ||
| 54 | Plainfield | New Jersey | United States | ||
| 55 | Somerville | New Jersey | United States | ||
| 56 | Summit | New Jersey | United States | ||
| 57 | Mineola | New York | United States | ||
| 58 | New York | New York | United States | ||
| 59 | Rochester | New York | United States | ||
| 60 | Asheboro | North Carolina | United States | ||
| 61 | Charlotte | North Carolina | United States | ||
| 62 | Pinehurst | North Carolina | United States | ||
| 63 | Winston-Salem | North Carolina | United States | ||
| 64 | Canton | Ohio | United States | ||
| 65 | Cleveland | Ohio | United States | ||
| 66 | Columbus | Ohio | United States | ||
| 67 | Bend | Oregon | United States | ||
| 68 | Bethlehem | Pennsylvania | United States | ||
| 69 | Pittsburgh | Pennsylvania | United States | ||
| 70 | Spartanburg | South Carolina | United States | ||
| 71 | Sioux Falls | South Dakota | United States | ||
| 72 | Chattanooga | Tennessee | United States | ||
| 73 | Nashville | Tennessee | United States | ||
| 74 | Arlington | Texas | United States | ||
| 75 | Edinburg | Texas | United States | ||
| 76 | Fort Sam Houston | Texas | United States | ||
| 77 | Fort Worth | Texas | United States | ||
| 78 | Houston | Texas | United States | ||
| 79 | Plano | Texas | United States | ||
| 80 | San Antonio | Texas | United States | ||
| 81 | Ogden | Utah | United States | ||
| 82 | Seattle | Washington | United States | ||
| 83 | Spokane | Washington | United States | ||
| 84 | Tacoma | Washington | United States | ||
| 85 | Box Hill | Australia | |||
| 86 | Fitzroy | Australia | |||
| 87 | Footscray | Australia | |||
| 88 | Kogarah | Australia | |||
| 89 | Kurralta Park | Australia | |||
| 90 | Nedlands | Australia | |||
| 91 | New South Wales | Australia | |||
| 92 | Woodville | Australia | |||
| 93 | Woolloongabba N/a | Australia | |||
| 94 | Innsbruck | Austria | |||
| 95 | Linz | Austria | |||
| 96 | Salzburg | Austria | |||
| 97 | Wien N/a | Austria | |||
| 98 | Wien Wien | Austria | |||
| 99 | Brugge | Belgium | |||
| 100 | Brussels | Belgium | |||
| 101 | Brussel | Belgium | |||
| 102 | Haine-saint-paul, LA Louviere | Belgium | |||
| 103 | Leuven | Belgium | |||
| 104 | Liege | Belgium | |||
| 105 | Calgary | Alberta | Canada | ||
| 106 | Toronto | Ontario | Canada | ||
| 107 | Montreal | Quebec | Canada | ||
| 108 | Montréal | Quebec | Canada | ||
| 109 | Greenfield Park | Canada | |||
| 110 | N/a N/a | Canada | |||
| 111 | Nova Scotia | Canada | |||
| 112 | Quebec | Canada | |||
| 113 | Aarhus C | Denmark | |||
| 114 | Odense | Denmark | |||
| 115 | Vejle | Denmark | |||
| 116 | Amiens N/a Picardie | France | |||
| 117 | Angers | France | |||
| 118 | Bayonne Cedex | France | |||
| 119 | Bretagne | France | |||
| 120 | Caen | France | |||
| 121 | Cergy Pontoise | France | |||
| 122 | Chalons Sur Saone | France | |||
| 123 | Clermont-Ferrand | France | |||
| 124 | Creteil | France | |||
| 125 | Dijon | France | |||
| 126 | Dunkerque Cedex 1 | France | |||
| 127 | Grenoble Cedex 9 | France | |||
| 128 | La Roche sur Yon Cedex 9 | France | |||
| 129 | Le Chesnay Cedex | France | |||
| 130 | Le Mans | France | |||
| 131 | Lille Cedex | France | |||
| 132 | Lille | France | |||
| 133 | Limoges | France | |||
| 134 | Lyon, Pierre-Benite | France | |||
| 135 | Marseille Cedex 9 | France | |||
| 136 | Metz-Tessy | France | |||
| 137 | Montivilliers | France | |||
| 138 | Montpellier | France | |||
| 139 | Mulhouse | France | |||
| 140 | Nantes | France | |||
| 141 | Nice N/a | France | |||
| 142 | Paris Cedex 12 | France | |||
| 143 | Paris, 75 | France | |||
| 144 | Paris | France | |||
| 145 | PERIGUEUX cedex | France | |||
| 146 | Perpignan | France | |||
| 147 | Pessac | France | |||
| 148 | Poitiers | France | |||
| 149 | Reims | France | |||
| 150 | Rennes | France | |||
| 151 | Rouen Cedex | France | |||
| 152 | Saint Brieuc Cedex 1 | France | |||
| 153 | Saint Priest en Jarez | France | |||
| 154 | St Malo Cedex | France | |||
| 155 | St Quentin Cedex | France | |||
| 156 | Strasbourg | France | |||
| 157 | Toulouse Cedex 9 | France | |||
| 158 | TOURS Cedex 9 | France | |||
| 159 | Vandoeuvre Les Nancy | France | |||
| 160 | Aschaffenburg | Germany | |||
| 161 | Bad Berka | Germany | |||
| 162 | Bonn | Germany | |||
| 163 | Braunschweig | Germany | |||
| 164 | Dresden | Germany | |||
| 165 | Essen | Germany | |||
| 166 | Frankfurt | Germany | |||
| 167 | Hannover | Germany | |||
| 168 | Heidelberg | Germany | |||
| 169 | Hessen | Germany | |||
| 170 | Kiel | Germany | |||
| 171 | Koblenz | Germany | |||
| 172 | Mainz | Germany | |||
| 173 | Mannheim | Germany | |||
| 174 | Rostock | Germany | |||
| 175 | Schwerin | Germany | |||
| 176 | Stuttgart | Germany | |||
| 177 | Tuebingen | Germany | |||
| 178 | Ulm | Germany | |||
| 179 | Villingen-Schwenningen | Germany | |||
| 180 | Dublin | Ireland | |||
| 181 | Galway | Ireland | |||
| 182 | Hadera | Israel | |||
| 183 | Haifa | Israel | |||
| 184 | Jerusalem | Israel | |||
| 185 | Nahariya | Israel | |||
| 186 | Petah Tikva | Israel | |||
| 187 | Tel-Aviv | Israel | |||
| 188 | Hilversum | Netherlands | |||
| 189 | Hoofddorp | Netherlands | |||
| 190 | Rotterdam | Netherlands | |||
| 191 | Tilburg | Netherlands | |||
| 192 | Falun | Sweden | |||
| 193 | Göteborg | Sweden | |||
| 194 | Halmstad | Sweden | |||
| 195 | Helsingborg | Sweden | |||
| 196 | Huddinge | Sweden | |||
| 197 | Lulea | Sweden | |||
| 198 | Lund | Sweden | |||
| 199 | Stockholm | Sweden | |||
| 200 | Örebro | Sweden | |||
| 201 | Aberdeen | United Kingdom | |||
| 202 | Canterbury | United Kingdom | |||
| 203 | Dundee | United Kingdom | |||
| 204 | Leeds | United Kingdom | |||
| 205 | London | United Kingdom | |||
| 206 | Manchester | United Kingdom | |||
| 207 | Nottingham | United Kingdom | |||
| 208 | Oxford | United Kingdom | |||
| 209 | Plymouth, Devon | United Kingdom | |||
| 210 | Southampton | United Kingdom | |||
| 211 | Truro | United Kingdom | |||
| 212 | Wolverhampton | United Kingdom |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- CR104762
- 54767414MMY3008
- 2014-002273-11
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity. | Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity. |
| Period Title: Overall Study | ||
| STARTED | 369 | 368 |
| Treated | 365 | 364 |
| COMPLETED | 90 | 69 |
| NOT COMPLETED | 279 | 299 |
Baseline Characteristics
| Arm/Group Title | Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) | Total |
|---|---|---|---|
| Arm/Group Description | Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity. | Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 369 | 368 | 737 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
74.2
(5.66)
|
74.0
(5.44)
|
74.1
(5.55)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
174
47.2%
|
179
48.6%
|
353
47.9%
|
| Male |
195
52.8%
|
189
51.4%
|
384
52.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
12
3.3%
|
11
3%
|
23
3.1%
|
| Not Hispanic or Latino |
352
95.4%
|
347
94.3%
|
699
94.8%
|
| Unknown or Not Reported |
5
1.4%
|
10
2.7%
|
15
2%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
0.5%
|
3
0.8%
|
5
0.7%
|
| Native Hawaiian or Other Pacific Islander |
1
0.3%
|
0
0%
|
1
0.1%
|
| Black or African American |
16
4.3%
|
12
3.3%
|
28
3.8%
|
| White |
339
91.9%
|
336
91.3%
|
675
91.6%
|
| Other |
6
1.6%
|
6
1.6%
|
12
1.6%
|
| Unknown or Not Reported |
5
1.4%
|
11
3%
|
16
2.2%
|
| Region of Enrollment (Count of Participants) | |||
| AUSTRALIA |
18
4.9%
|
17
4.6%
|
35
4.7%
|
| AUSTRIA |
11
3%
|
3
0.8%
|
14
1.9%
|
| BELGIUM |
5
1.4%
|
2
0.5%
|
7
0.9%
|
| CANADA |
28
7.6%
|
24
6.5%
|
52
7.1%
|
| DENMARK |
6
1.6%
|
10
2.7%
|
16
2.2%
|
| FRANCE |
155
42%
|
157
42.7%
|
312
42.3%
|
| GERMANY |
16
4.3%
|
19
5.2%
|
35
4.7%
|
| IRELAND |
3
0.8%
|
4
1.1%
|
7
0.9%
|
| ISRAEL |
3
0.8%
|
5
1.4%
|
8
1.1%
|
| ITALY |
3
0.8%
|
3
0.8%
|
6
0.8%
|
| NETHERLANDS |
1
0.3%
|
4
1.1%
|
5
0.7%
|
| SWEDEN |
12
3.3%
|
10
2.7%
|
22
3%
|
| UNITED KINGDOM |
34
9.2%
|
33
9%
|
67
9.1%
|
| UNITED STATES |
74
20.1%
|
77
20.9%
|
151
20.5%
|
| Stage of Disease (ISS) (Count of Participants) | |||
| Stage I |
103
27.9%
|
98
26.6%
|
201
27.3%
|
| Stage II |
156
42.3%
|
163
44.3%
|
319
43.3%
|
| Stage III |
110
29.8%
|
107
29.1%
|
217
29.4%
|
| Time from Multiple Myeloma (MM) diagnosis (months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [months] |
1.3
(1.4)
|
1.4
(1.5)
|
1.3
(1.5)
|
Outcome Measures
| Title | Primary: Progression-free Survival (PFS) |
|---|---|
| Description | PFS is defined as time from date of randomization to either progressive disease (PD) or death, whichever occurs first based on computerized algorithm as per International Myeloma Working Group (IMWG) criteria. PD is defined as an increase of 25 percent (%) from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than [>]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 Plasma cell (PC) proliferative disorder. |
| Time Frame | From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or clinical cut-off (CCO) whichever occurs first (up to 3.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants. |
| Arm/Group Title | Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity. | Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity. |
| Measure Participants | 369 | 368 |
| Median (95% Confidence Interval) [Months] |
31.87
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lenalidomide + Dexamethasone (Rd), Daratumumab + Lenalidomide + Dexamethasone (DRd) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% 0.43 to 0.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Complete Response (CR) or Better |
|---|---|
| Description | CR or better is defined as percentage of participants with a CR or better (CR or stringent complete response [sCR]) based on computerized algorithm as per IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. In participants with only measurable disease by serum FLC levels a normal serum FLC ratio is required. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. |
| Time Frame | From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Participants With Very Good Partial Response (VGPR) or Better |
|---|---|
| Description | VGPR or better is defined as the percentage of participants with a response of VGPR or better (VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. In participants with only measurable disease by serum FLC levels a >90% decrease in the difference between involved and uninvolved FLC levels is required. |
| Time Frame | From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Participants With Negative Minimal Residual Disease (MRD) |
|---|---|
| Description | MRD negativity rate is defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the date of randomization by evaluation of bone marrow aspirates. MRD was assessed in participants who achieved CR or better. |
| Time Frame | From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR is defined as the percentage of participants who achieved partial response (PR) or better (PR, VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. PR is defined as >=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. A >=50% reduction in the size of soft tissue plasmacytomas is also required. |
| Time Frame | From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was measured from the date of randomization to the date of the death. |
| Time Frame | From randomization to death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Disease Progression (TTP) |
|---|---|
| Description | TTP is defined as the time from the date of randomization to the date of PD based on computerized algorithm as per IMWG criteria, or death due to PD. |
| Time Frame | From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Response |
|---|---|
| Description | Time to response is defined as the time from the date of randomization to the first efficacy evaluation that met criteria for PR or better based on computerized algorithm as per IMWG criteria. 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. A >=50% reduction in the size of soft tissue plasmacytomas is also required. |
| Time Frame | From randomization to first response (PR or better) (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Duration of Response (DoR) |
|---|---|
| Description | DoR is defined as the time from the date of initial response (PR or better) to the date of PD, based on computerized algorithm as per IMWG criteria. |
| Time Frame | From first response (PR of better) to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Subsequent Anti-myeloma Treatment |
|---|---|
| Description | Time to subsequent anti-myeloma treatment is defined as the time from randomization to the start of first line of subsequent anti-myeloma treatment or death, whichever occurs first. |
| Time Frame | From randomization to start of first subsequent anti-myeloma treatment, death, withdrawal of consent to study participation or CCO whichever is first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Progression-free Survival on Next Line of Therapy (PFS2) |
|---|---|
| Description | PFS2 is defined as the time from randomization to progression on the first line of subsequent anti-myeloma therapy or death, whichever occurs first. Disease progression on first line of subsequent anti-myeloma treatment was based on investigator judgment. Participants that were censored for PFS1 were also censored for PFS2. |
| Time Frame | From randomization to disease progression on first line of subsequent anti-myeloma therapy, death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Global Health Status Score to Day 1 of Cycle 3, 6, 9 and 12 |
|---|---|
| Description | EORTC QLQ-C30 is 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms. |
| Time Frame | Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable in this outcome measure. Here 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. |
| Arm/Group Title | Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity. | Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity. |
| Measure Participants | 348 | 354 |
| Global health status score: Cycle 3 Day 1 |
1.5
|
4.5
|
| Global health status score: Cycle 6 Day 1 |
5.6
|
6.4
|
| Global health status score: Cycle 9 Day 1 |
7
|
8.2
|
| Global health status score: Cycle 12 Day 1 |
5.4
|
8.4
|
| Title | Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) to Day 1 of Cycle 3, 6, 9 and 12 |
|---|---|
| Description | EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. |
| Time Frame | Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable in this outcome measure. Here 'n' signifies number of participants analyzed at specified timepoints. |
| Arm/Group Title | Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity. | Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity. |
| Measure Participants | 346 | 349 |
| Change at Cycle 3 Day 1 |
2.5
|
4.9
|
| Change at Cycle 6 Day 1 |
5.7
|
8
|
| Change at Cycle 9 Day 1 |
7.7
|
10.2
|
| Change at Cycle 12 Day 1 |
4.9
|
10.1
|
| Title | Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score to Day 1 of Cycle 3, 6, 9 and 12 |
|---|---|
| Description | EQ-5D-5L is standardized, participant-reported questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5-dimension scores were combined and converted into single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of individual (but allows for values less than 0 by United kingdom [UK] scoring algorithm). |
| Time Frame | Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable in this outcome measure. Here 'n' signifies number of participants analyzed at specified timepoints. |
| Arm/Group Title | Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity. | Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity. |
| Measure Participants | 346 | 349 |
| Change at Cycle 3 Day 1 |
0.08
|
0.107
|
| Change at Cycle 6 Day 1 |
0.116
|
0.136
|
| Change at Cycle 9 Day 1 |
0.124
|
0.124
|
| Change at Cycle 12 Day 1 |
0.113
|
0.141
|
Adverse Events
| Time Frame | Up to 3.5 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population was defined as participants who have received at least 1 administration of any study treatment (partial or complete). | |||
| Arm/Group Title | Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) | ||
| Arm/Group Description | Participants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity. | Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity. | ||
All Cause Mortality |
||||
| Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 76/365 (20.8%) | 62/364 (17%) | ||
Serious Adverse Events |
||||
| Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 229/365 (62.7%) | 229/364 (62.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 12/365 (3.3%) | 6/364 (1.6%) | ||
| Anaemia Macrocytic | 1/365 (0.3%) | 0/364 (0%) | ||
| Disseminated Intravascular Coagulation | 1/365 (0.3%) | 0/364 (0%) | ||
| Febrile Neutropenia | 9/365 (2.5%) | 9/364 (2.5%) | ||
| Heparin-Induced Thrombocytopenia | 1/365 (0.3%) | 0/364 (0%) | ||
| Leukopenia | 0/365 (0%) | 1/364 (0.3%) | ||
| Neutropenia | 2/365 (0.5%) | 3/364 (0.8%) | ||
| Thrombocytopenia | 2/365 (0.5%) | 0/364 (0%) | ||
| Cardiac disorders | ||||
| Acute Coronary Syndrome | 5/365 (1.4%) | 0/364 (0%) | ||
| Acute Myocardial Infarction | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Angina Pectoris | 0/365 (0%) | 2/364 (0.5%) | ||
| Arrhythmia | 1/365 (0.3%) | 0/364 (0%) | ||
| Arteriosclerosis Coronary Artery | 0/365 (0%) | 1/364 (0.3%) | ||
| Atrial Fibrillation | 12/365 (3.3%) | 8/364 (2.2%) | ||
| Atrial Flutter | 2/365 (0.5%) | 2/364 (0.5%) | ||
| Atrial Tachycardia | 1/365 (0.3%) | 0/364 (0%) | ||
| Atrioventricular Block | 0/365 (0%) | 1/364 (0.3%) | ||
| Atrioventricular Block Complete | 1/365 (0.3%) | 0/364 (0%) | ||
| Bradycardia | 1/365 (0.3%) | 0/364 (0%) | ||
| Cardiac Amyloidosis | 1/365 (0.3%) | 0/364 (0%) | ||
| Cardiac Arrest | 3/365 (0.8%) | 2/364 (0.5%) | ||
| Cardiac Failure | 9/365 (2.5%) | 5/364 (1.4%) | ||
| Cardiac Failure Acute | 0/365 (0%) | 1/364 (0.3%) | ||
| Cardiac Failure Chronic | 1/365 (0.3%) | 0/364 (0%) | ||
| Cardiac Failure Congestive | 5/365 (1.4%) | 2/364 (0.5%) | ||
| Cardio-Respiratory Arrest | 0/365 (0%) | 1/364 (0.3%) | ||
| Cardiogenic Shock | 1/365 (0.3%) | 0/364 (0%) | ||
| Coronary Artery Disease | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Coronary Artery Stenosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Hypertensive Heart Disease | 0/365 (0%) | 1/364 (0.3%) | ||
| Myocardial Infarction | 5/365 (1.4%) | 1/364 (0.3%) | ||
| Myocardial Ischaemia | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Myocarditis | 1/365 (0.3%) | 0/364 (0%) | ||
| Pericardial Effusion | 0/365 (0%) | 1/364 (0.3%) | ||
| Stress Cardiomyopathy | 0/365 (0%) | 1/364 (0.3%) | ||
| Ventricular Tachycardia | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Congenital, familial and genetic disorders | ||||
| Corneal Dystrophy | 0/365 (0%) | 1/364 (0.3%) | ||
| Ear and labyrinth disorders | ||||
| Deafness Bilateral | 0/365 (0%) | 1/364 (0.3%) | ||
| Vertigo | 2/365 (0.5%) | 2/364 (0.5%) | ||
| Endocrine disorders | ||||
| Adrenal Insufficiency | 0/365 (0%) | 1/364 (0.3%) | ||
| Hypothyroidism | 1/365 (0.3%) | 0/364 (0%) | ||
| Eye disorders | ||||
| Blepharitis | 0/365 (0%) | 1/364 (0.3%) | ||
| Cataract | 5/365 (1.4%) | 2/364 (0.5%) | ||
| Retinal Artery Occlusion | 0/365 (0%) | 1/364 (0.3%) | ||
| Retinal Detachment | 1/365 (0.3%) | 0/364 (0%) | ||
| Retinal Vein Thrombosis | 1/365 (0.3%) | 0/364 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 2/365 (0.5%) | 4/364 (1.1%) | ||
| Abdominal Pain Upper | 0/365 (0%) | 1/364 (0.3%) | ||
| Ascites | 0/365 (0%) | 2/364 (0.5%) | ||
| Colitis | 3/365 (0.8%) | 1/364 (0.3%) | ||
| Colitis Ischaemic | 0/365 (0%) | 3/364 (0.8%) | ||
| Constipation | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Diarrhoea | 6/365 (1.6%) | 9/364 (2.5%) | ||
| Diarrhoea Haemorrhagic | 1/365 (0.3%) | 0/364 (0%) | ||
| Diverticular Perforation | 2/365 (0.5%) | 4/364 (1.1%) | ||
| Diverticulum | 1/365 (0.3%) | 0/364 (0%) | ||
| Diverticulum Intestinal Haemorrhagic | 1/365 (0.3%) | 0/364 (0%) | ||
| Dyspepsia | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Dysphagia | 0/365 (0%) | 1/364 (0.3%) | ||
| Enterovesical Fistula | 1/365 (0.3%) | 0/364 (0%) | ||
| Faecaloma | 2/365 (0.5%) | 0/364 (0%) | ||
| Gastric Haemorrhage | 1/365 (0.3%) | 0/364 (0%) | ||
| Gastric Ulcer | 1/365 (0.3%) | 0/364 (0%) | ||
| Gastrointestinal Haemorrhage | 2/365 (0.5%) | 2/364 (0.5%) | ||
| Inguinal Hernia | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Inguinal Hernia Strangulated | 1/365 (0.3%) | 0/364 (0%) | ||
| Intestinal Ischaemia | 0/365 (0%) | 1/364 (0.3%) | ||
| Intestinal Obstruction | 0/365 (0%) | 2/364 (0.5%) | ||
| Large Intestinal Obstruction | 1/365 (0.3%) | 0/364 (0%) | ||
| Large Intestine Perforation | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Melaena | 2/365 (0.5%) | 0/364 (0%) | ||
| Nausea | 2/365 (0.5%) | 4/364 (1.1%) | ||
| Oesophageal Achalasia | 0/365 (0%) | 1/364 (0.3%) | ||
| Oesophagitis | 1/365 (0.3%) | 0/364 (0%) | ||
| Pancreatitis | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Pancreatitis Acute | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Pneumoperitoneum | 1/365 (0.3%) | 0/364 (0%) | ||
| Rectal Haemorrhage | 2/365 (0.5%) | 0/364 (0%) | ||
| Small Intestinal Obstruction | 0/365 (0%) | 1/364 (0.3%) | ||
| Subileus | 1/365 (0.3%) | 0/364 (0%) | ||
| Upper Gastrointestinal Haemorrhage | 0/365 (0%) | 1/364 (0.3%) | ||
| Vomiting | 3/365 (0.8%) | 4/364 (1.1%) | ||
| General disorders | ||||
| Asthenia | 7/365 (1.9%) | 3/364 (0.8%) | ||
| Chest Discomfort | 1/365 (0.3%) | 0/364 (0%) | ||
| Chest Pain | 2/365 (0.5%) | 0/364 (0%) | ||
| Chills | 0/365 (0%) | 1/364 (0.3%) | ||
| Extravasation | 0/365 (0%) | 1/364 (0.3%) | ||
| Fatigue | 0/365 (0%) | 4/364 (1.1%) | ||
| General Physical Health Deterioration | 10/365 (2.7%) | 2/364 (0.5%) | ||
| Granuloma | 0/365 (0%) | 1/364 (0.3%) | ||
| Malaise | 1/365 (0.3%) | 0/364 (0%) | ||
| Multiple Organ Dysfunction Syndrome | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Non-Cardiac Chest Pain | 3/365 (0.8%) | 3/364 (0.8%) | ||
| Oedema Peripheral | 0/365 (0%) | 1/364 (0.3%) | ||
| Pain | 1/365 (0.3%) | 0/364 (0%) | ||
| Peripheral Swelling | 0/365 (0%) | 1/364 (0.3%) | ||
| Pyrexia | 11/365 (3%) | 16/364 (4.4%) | ||
| Sudden Cardiac Death | 1/365 (0.3%) | 0/364 (0%) | ||
| Sudden Death | 0/365 (0%) | 1/364 (0.3%) | ||
| Systemic Inflammatory Response Syndrome | 1/365 (0.3%) | 0/364 (0%) | ||
| Hepatobiliary disorders | ||||
| Acute Hepatic Failure | 1/365 (0.3%) | 0/364 (0%) | ||
| Bile Duct Stone | 0/365 (0%) | 1/364 (0.3%) | ||
| Cholecystitis | 1/365 (0.3%) | 0/364 (0%) | ||
| Cholecystitis Acute | 0/365 (0%) | 4/364 (1.1%) | ||
| Cholestasis | 1/365 (0.3%) | 0/364 (0%) | ||
| Hepatic Failure | 1/365 (0.3%) | 0/364 (0%) | ||
| Hepatocellular Injury | 1/365 (0.3%) | 0/364 (0%) | ||
| Hyperbilirubinaemia | 1/365 (0.3%) | 0/364 (0%) | ||
| Infections and infestations | ||||
| Abdominal Sepsis | 1/365 (0.3%) | 0/364 (0%) | ||
| Anal Abscess | 1/365 (0.3%) | 0/364 (0%) | ||
| Appendicitis Perforated | 1/365 (0.3%) | 0/364 (0%) | ||
| Arthritis Bacterial | 1/365 (0.3%) | 0/364 (0%) | ||
| Arthritis Infective | 0/365 (0%) | 1/364 (0.3%) | ||
| Bacteraemia | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Bacterial Diarrhoea | 0/365 (0%) | 1/364 (0.3%) | ||
| Bronchiolitis | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Bronchitis | 5/365 (1.4%) | 12/364 (3.3%) | ||
| Campylobacter Infection | 1/365 (0.3%) | 0/364 (0%) | ||
| Cellulitis | 4/365 (1.1%) | 2/364 (0.5%) | ||
| Clostridium Difficile Colitis | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Colonic Abscess | 0/365 (0%) | 1/364 (0.3%) | ||
| Corona Virus Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Cystitis | 0/365 (0%) | 1/364 (0.3%) | ||
| Device Related Infection | 0/365 (0%) | 3/364 (0.8%) | ||
| Diverticulitis | 3/365 (0.8%) | 6/364 (1.6%) | ||
| Endocarditis | 0/365 (0%) | 1/364 (0.3%) | ||
| Endocarditis Staphylococcal | 1/365 (0.3%) | 0/364 (0%) | ||
| Erysipelas | 3/365 (0.8%) | 3/364 (0.8%) | ||
| Escherichia Pyelonephritis | 1/365 (0.3%) | 0/364 (0%) | ||
| Escherichia Sepsis | 2/365 (0.5%) | 0/364 (0%) | ||
| Escherichia Urinary Tract Infection | 0/365 (0%) | 2/364 (0.5%) | ||
| Gastroenteritis | 0/365 (0%) | 1/364 (0.3%) | ||
| Gastrointestinal Viral Infection | 1/365 (0.3%) | 0/364 (0%) | ||
| Groin Abscess | 2/365 (0.5%) | 0/364 (0%) | ||
| Haematoma Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Infected Cyst | 1/365 (0.3%) | 0/364 (0%) | ||
| Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Influenza | 6/365 (1.6%) | 11/364 (3%) | ||
| Klebsiella Bacteraemia | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Klebsiella Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Laryngitis | 1/365 (0.3%) | 0/364 (0%) | ||
| Lower Respiratory Tract Infection | 11/365 (3%) | 10/364 (2.7%) | ||
| Lower Respiratory Tract Infection Bacterial | 2/365 (0.5%) | 0/364 (0%) | ||
| Lower Respiratory Tract Infection Viral | 1/365 (0.3%) | 0/364 (0%) | ||
| Lung Infection | 1/365 (0.3%) | 7/364 (1.9%) | ||
| Metapneumovirus Infection | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Myocarditis Infectious | 0/365 (0%) | 1/364 (0.3%) | ||
| Neutropenic Infection | 1/365 (0.3%) | 0/364 (0%) | ||
| Neutropenic Sepsis | 0/365 (0%) | 1/364 (0.3%) | ||
| Nocardiosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Oesophageal Candidiasis | 0/365 (0%) | 1/364 (0.3%) | ||
| Osteomyelitis | 2/365 (0.5%) | 0/364 (0%) | ||
| Otitis Externa | 1/365 (0.3%) | 0/364 (0%) | ||
| Peritonitis | 1/365 (0.3%) | 0/364 (0%) | ||
| Pharyngitis | 0/365 (0%) | 1/364 (0.3%) | ||
| Pleural Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Pneumocystis Jirovecii Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Pneumocystis Jirovecii Pneumonia | 0/365 (0%) | 1/364 (0.3%) | ||
| Pneumonia | 27/365 (7.4%) | 48/364 (13.2%) | ||
| Pulmonary Mycosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Pyelonephritis | 0/365 (0%) | 2/364 (0.5%) | ||
| Respiratory Syncytial Virus Bronchiolitis | 1/365 (0.3%) | 0/364 (0%) | ||
| Respiratory Syncytial Virus Infection | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Respiratory Tract Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Salmonellosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Sepsis | 7/365 (1.9%) | 9/364 (2.5%) | ||
| Sepsis Syndrome | 0/365 (0%) | 1/364 (0.3%) | ||
| Septic Arthritis Staphylococcal | 0/365 (0%) | 1/364 (0.3%) | ||
| Septic Embolus | 0/365 (0%) | 1/364 (0.3%) | ||
| Septic Shock | 3/365 (0.8%) | 4/364 (1.1%) | ||
| Skin Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Soft Tissue Infection | 1/365 (0.3%) | 0/364 (0%) | ||
| Spinal Cord Infection | 1/365 (0.3%) | 0/364 (0%) | ||
| Staphylococcal Sepsis | 1/365 (0.3%) | 0/364 (0%) | ||
| Subcutaneous Abscess | 0/365 (0%) | 1/364 (0.3%) | ||
| Upper Respiratory Tract Infection | 4/365 (1.1%) | 5/364 (1.4%) | ||
| Ureteritis | 0/365 (0%) | 1/364 (0.3%) | ||
| Urinary Tract Infection | 5/365 (1.4%) | 8/364 (2.2%) | ||
| Urinary Tract Infection Bacterial | 0/365 (0%) | 1/364 (0.3%) | ||
| Urosepsis | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Varicella Zoster Virus Infection | 1/365 (0.3%) | 0/364 (0%) | ||
| Vascular Stent Infection | 0/365 (0%) | 1/364 (0.3%) | ||
| Vestibular Neuronitis | 0/365 (0%) | 1/364 (0.3%) | ||
| Viral Upper Respiratory Tract Infection | 0/365 (0%) | 2/364 (0.5%) | ||
| Injury, poisoning and procedural complications | ||||
| Accident | 0/365 (0%) | 1/364 (0.3%) | ||
| Accidental Overdose | 1/365 (0.3%) | 0/364 (0%) | ||
| Acetabulum Fracture | 0/365 (0%) | 1/364 (0.3%) | ||
| Clavicle Fracture | 0/365 (0%) | 1/364 (0.3%) | ||
| Concussion | 0/365 (0%) | 1/364 (0.3%) | ||
| Craniocerebral Injury | 0/365 (0%) | 1/364 (0.3%) | ||
| Face Injury | 0/365 (0%) | 1/364 (0.3%) | ||
| Facial Bones Fracture | 0/365 (0%) | 1/364 (0.3%) | ||
| Fall | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Femoral Neck Fracture | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Femur Fracture | 3/365 (0.8%) | 4/364 (1.1%) | ||
| Foot Fracture | 1/365 (0.3%) | 0/364 (0%) | ||
| Fracture | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Head Injury | 1/365 (0.3%) | 0/364 (0%) | ||
| Hip Fracture | 1/365 (0.3%) | 4/364 (1.1%) | ||
| Humerus Fracture | 0/365 (0%) | 2/364 (0.5%) | ||
| Limb Injury | 1/365 (0.3%) | 0/364 (0%) | ||
| Open Fracture | 1/365 (0.3%) | 0/364 (0%) | ||
| Pelvic Fracture | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Periorbital Haemorrhage | 0/365 (0%) | 1/364 (0.3%) | ||
| Postoperative Fever | 1/365 (0.3%) | 0/364 (0%) | ||
| Pubis Fracture | 1/365 (0.3%) | 0/364 (0%) | ||
| Rib Fracture | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Spinal Compression Fracture | 2/365 (0.5%) | 6/364 (1.6%) | ||
| Spinal Fracture | 1/365 (0.3%) | 0/364 (0%) | ||
| Sternal Fracture | 1/365 (0.3%) | 0/364 (0%) | ||
| Subdural Haematoma | 0/365 (0%) | 1/364 (0.3%) | ||
| Tendon Rupture | 0/365 (0%) | 1/364 (0.3%) | ||
| Upper Limb Fracture | 0/365 (0%) | 2/364 (0.5%) | ||
| Investigations | ||||
| Blood Creatinine Increased | 2/365 (0.5%) | 0/364 (0%) | ||
| C-Reactive Protein Increased | 1/365 (0.3%) | 1/364 (0.3%) | ||
| International Normalised Ratio Increased | 1/365 (0.3%) | 0/364 (0%) | ||
| Lipase Increased | 0/365 (0%) | 1/364 (0.3%) | ||
| Occult Blood Positive | 1/365 (0.3%) | 0/364 (0%) | ||
| Oxygen Saturation Decreased | 0/365 (0%) | 1/364 (0.3%) | ||
| Transaminases Increased | 1/365 (0.3%) | 0/364 (0%) | ||
| Troponin I Increased | 1/365 (0.3%) | 0/364 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Dehydration | 1/365 (0.3%) | 6/364 (1.6%) | ||
| Diabetes Mellitus Inadequate Control | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Failure to Thrive | 1/365 (0.3%) | 0/364 (0%) | ||
| Gout | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Hypercalcaemia | 3/365 (0.8%) | 1/364 (0.3%) | ||
| Hyperglycaemia | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Hyperkalaemia | 2/365 (0.5%) | 2/364 (0.5%) | ||
| Hypocalcaemia | 3/365 (0.8%) | 1/364 (0.3%) | ||
| Hypokalaemia | 5/365 (1.4%) | 3/364 (0.8%) | ||
| Hypomagnesaemia | 1/365 (0.3%) | 0/364 (0%) | ||
| Hyponatraemia | 3/365 (0.8%) | 2/364 (0.5%) | ||
| Hypovolaemia | 1/365 (0.3%) | 0/364 (0%) | ||
| Type 1 Diabetes Mellitus | 0/365 (0%) | 1/364 (0.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/365 (0.5%) | 2/364 (0.5%) | ||
| Arthritis | 0/365 (0%) | 2/364 (0.5%) | ||
| Back Pain | 8/365 (2.2%) | 12/364 (3.3%) | ||
| Bone Lesion | 2/365 (0.5%) | 0/364 (0%) | ||
| Bone Pain | 4/365 (1.1%) | 4/364 (1.1%) | ||
| Bursitis | 1/365 (0.3%) | 0/364 (0%) | ||
| Chondrocalcinosis | 1/365 (0.3%) | 0/364 (0%) | ||
| Chondrocalcinosis Pyrophosphate | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Crystal Arthropathy | 1/365 (0.3%) | 0/364 (0%) | ||
| Intervertebral Disc Compression | 0/365 (0%) | 1/364 (0.3%) | ||
| Intervertebral Disc Protrusion | 0/365 (0%) | 1/364 (0.3%) | ||
| Jaw Fistula | 1/365 (0.3%) | 0/364 (0%) | ||
| Lumbar Spinal Stenosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Muscle Spasms | 0/365 (0%) | 2/364 (0.5%) | ||
| Muscular Weakness | 2/365 (0.5%) | 4/364 (1.1%) | ||
| Musculoskeletal Chest Pain | 2/365 (0.5%) | 0/364 (0%) | ||
| Musculoskeletal Pain | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Neck Pain | 1/365 (0.3%) | 0/364 (0%) | ||
| Osteoarthritis | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Osteolysis | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Osteonecrosis | 0/365 (0%) | 2/364 (0.5%) | ||
| Osteonecrosis of Jaw | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Osteoporosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Pain in Extremity | 0/365 (0%) | 1/364 (0.3%) | ||
| Pathological Fracture | 1/365 (0.3%) | 0/364 (0%) | ||
| Primary Sequestrum | 1/365 (0.3%) | 0/364 (0%) | ||
| Spinal Pain | 4/365 (1.1%) | 2/364 (0.5%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma Gastric | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Adrenal Adenoma | 1/365 (0.3%) | 0/364 (0%) | ||
| Basal Cell Carcinoma | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Breast Cancer | 1/365 (0.3%) | 0/364 (0%) | ||
| Cancer Pain | 1/365 (0.3%) | 0/364 (0%) | ||
| Colorectal Adenocarcinoma | 0/365 (0%) | 1/364 (0.3%) | ||
| Diffuse Large B-Cell Lymphoma | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Gastrointestinal Neoplasm | 1/365 (0.3%) | 0/364 (0%) | ||
| Gastrointestinal Stromal Tumour | 0/365 (0%) | 1/364 (0.3%) | ||
| Invasive Lobular Breast Carcinoma | 0/365 (0%) | 1/364 (0.3%) | ||
| Keratoacanthoma | 1/365 (0.3%) | 0/364 (0%) | ||
| Leiomyosarcoma | 1/365 (0.3%) | 0/364 (0%) | ||
| Lung Neoplasm Malignant | 1/365 (0.3%) | 0/364 (0%) | ||
| Mantle Cell Lymphoma | 0/365 (0%) | 1/364 (0.3%) | ||
| Meningioma | 0/365 (0%) | 1/364 (0.3%) | ||
| Neuroendocrine Carcinoma of the Skin | 1/365 (0.3%) | 0/364 (0%) | ||
| Porocarcinoma | 0/365 (0%) | 1/364 (0.3%) | ||
| Prostate Cancer | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Prostatic Adenoma | 1/365 (0.3%) | 0/364 (0%) | ||
| Small Cell Lung Cancer | 1/365 (0.3%) | 0/364 (0%) | ||
| Squamous Cell Carcinoma of Skin | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Transitional Cell Carcinoma | 1/365 (0.3%) | 0/364 (0%) | ||
| Nervous system disorders | ||||
| Brain Stem Infarction | 1/365 (0.3%) | 0/364 (0%) | ||
| Cerebral Infarction | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Cerebrovascular Accident | 5/365 (1.4%) | 5/364 (1.4%) | ||
| Cognitive Disorder | 0/365 (0%) | 1/364 (0.3%) | ||
| Dementia Alzheimer's Type | 1/365 (0.3%) | 0/364 (0%) | ||
| Dizziness | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Epilepsy | 0/365 (0%) | 1/364 (0.3%) | ||
| Focal Dyscognitive Seizures | 0/365 (0%) | 1/364 (0.3%) | ||
| Generalised Tonic-Clonic Seizure | 1/365 (0.3%) | 0/364 (0%) | ||
| Haemorrhage Intracranial | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Haemorrhagic Stroke | 0/365 (0%) | 1/364 (0.3%) | ||
| Headache | 0/365 (0%) | 1/364 (0.3%) | ||
| Hepatic Encephalopathy | 0/365 (0%) | 1/364 (0.3%) | ||
| Hyperaesthesia | 1/365 (0.3%) | 0/364 (0%) | ||
| Hypoaesthesia | 0/365 (0%) | 1/364 (0.3%) | ||
| Ischaemic Stroke | 3/365 (0.8%) | 1/364 (0.3%) | ||
| Nervous System Disorder | 0/365 (0%) | 1/364 (0.3%) | ||
| Neuralgia | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Orthostatic Intolerance | 0/365 (0%) | 1/364 (0.3%) | ||
| Peripheral Motor Neuropathy | 0/365 (0%) | 1/364 (0.3%) | ||
| Post Herpetic Neuralgia | 0/365 (0%) | 1/364 (0.3%) | ||
| Presyncope | 2/365 (0.5%) | 0/364 (0%) | ||
| Sciatica | 2/365 (0.5%) | 2/364 (0.5%) | ||
| Seizure | 2/365 (0.5%) | 3/364 (0.8%) | ||
| Spinal Cord Compression | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Syncope | 3/365 (0.8%) | 4/364 (1.1%) | ||
| Transient Ischaemic Attack | 3/365 (0.8%) | 0/364 (0%) | ||
| Vith Nerve Paralysis | 1/365 (0.3%) | 0/364 (0%) | ||
| Product Issues | ||||
| Device Dislocation | 1/365 (0.3%) | 0/364 (0%) | ||
| Psychiatric disorders | ||||
| Confusional State | 2/365 (0.5%) | 3/364 (0.8%) | ||
| Depression | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Eating Disorder | 1/365 (0.3%) | 0/364 (0%) | ||
| Major Depression | 1/365 (0.3%) | 0/364 (0%) | ||
| Mental Status Changes | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Personality Change | 1/365 (0.3%) | 0/364 (0%) | ||
| Psychotic Disorder | 0/365 (0%) | 1/364 (0.3%) | ||
| Renal and urinary disorders | ||||
| Acute Kidney Injury | 14/365 (3.8%) | 11/364 (3%) | ||
| Bladder Stenosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Chronic Kidney Disease | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Dysuria | 0/365 (0%) | 1/364 (0.3%) | ||
| Haematuria | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Renal Disorder | 0/365 (0%) | 1/364 (0.3%) | ||
| Renal Failure | 5/365 (1.4%) | 4/364 (1.1%) | ||
| Renal Impairment | 2/365 (0.5%) | 0/364 (0%) | ||
| Urethral Caruncle | 0/365 (0%) | 1/364 (0.3%) | ||
| Urinary Retention | 3/365 (0.8%) | 2/364 (0.5%) | ||
| Reproductive system and breast disorders | ||||
| Benign Prostatic Hyperplasia | 0/365 (0%) | 1/364 (0.3%) | ||
| Genital Prolapse | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Pelvic Pain | 1/365 (0.3%) | 0/364 (0%) | ||
| Vaginal Haemorrhage | 0/365 (0%) | 1/364 (0.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Pulmonary Oedema | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Asthma | 1/365 (0.3%) | 3/364 (0.8%) | ||
| Bronchiectasis | 1/365 (0.3%) | 0/364 (0%) | ||
| Bronchopneumopathy | 0/365 (0%) | 1/364 (0.3%) | ||
| Bronchospasm | 0/365 (0%) | 1/364 (0.3%) | ||
| Chronic Obstructive Pulmonary Disease | 3/365 (0.8%) | 1/364 (0.3%) | ||
| Dyspnoea | 4/365 (1.1%) | 6/364 (1.6%) | ||
| Epistaxis | 0/365 (0%) | 1/364 (0.3%) | ||
| Haemoptysis | 1/365 (0.3%) | 0/364 (0%) | ||
| Hiccups | 1/365 (0.3%) | 0/364 (0%) | ||
| Hypoxia | 2/365 (0.5%) | 4/364 (1.1%) | ||
| Lung Disorder | 1/365 (0.3%) | 0/364 (0%) | ||
| Pleural Effusion | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Pleurisy | 0/365 (0%) | 1/364 (0.3%) | ||
| Pleuritic Pain | 2/365 (0.5%) | 0/364 (0%) | ||
| Pneumonitis | 1/365 (0.3%) | 0/364 (0%) | ||
| Pulmonary Embolism | 14/365 (3.8%) | 11/364 (3%) | ||
| Pulmonary Thrombosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Respiratory Distress | 0/365 (0%) | 1/364 (0.3%) | ||
| Respiratory Failure | 1/365 (0.3%) | 0/364 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acute Febrile Neutrophilic Dermatosis | 1/365 (0.3%) | 0/364 (0%) | ||
| Dermatitis Exfoliative | 1/365 (0.3%) | 0/364 (0%) | ||
| Drug Reaction with Eosinophilia and Systemic Symptoms | 4/365 (1.1%) | 0/364 (0%) | ||
| Ecchymosis | 1/365 (0.3%) | 0/364 (0%) | ||
| Purpura | 1/365 (0.3%) | 1/364 (0.3%) | ||
| Rash | 1/365 (0.3%) | 0/364 (0%) | ||
| Rash Generalised | 5/365 (1.4%) | 0/364 (0%) | ||
| Rash Maculo-Papular | 0/365 (0%) | 1/364 (0.3%) | ||
| Skin Ulcer | 1/365 (0.3%) | 0/364 (0%) | ||
| Stevens-Johnson Syndrome | 1/365 (0.3%) | 0/364 (0%) | ||
| Vascular disorders | ||||
| Air Embolism | 0/365 (0%) | 1/364 (0.3%) | ||
| Aortic Aneurysm | 0/365 (0%) | 1/364 (0.3%) | ||
| Aortic Aneurysm Rupture | 1/365 (0.3%) | 0/364 (0%) | ||
| Arteritis | 1/365 (0.3%) | 0/364 (0%) | ||
| Deep Vein Thrombosis | 8/365 (2.2%) | 5/364 (1.4%) | ||
| Embolism | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Haematoma | 3/365 (0.8%) | 1/364 (0.3%) | ||
| Haemorrhage | 0/365 (0%) | 1/364 (0.3%) | ||
| Hypertension | 0/365 (0%) | 3/364 (0.8%) | ||
| Hypotension | 1/365 (0.3%) | 2/364 (0.5%) | ||
| Orthostatic Hypotension | 1/365 (0.3%) | 0/364 (0%) | ||
| Peripheral Arterial Occlusive Disease | 1/365 (0.3%) | 0/364 (0%) | ||
| Peripheral Artery Stenosis | 0/365 (0%) | 1/364 (0.3%) | ||
| Peripheral Ischaemia | 0/365 (0%) | 2/364 (0.5%) | ||
| Phlebitis | 2/365 (0.5%) | 1/364 (0.3%) | ||
| Superior Vena Cava Occlusion | 0/365 (0%) | 1/364 (0.3%) | ||
| Venous Thrombosis | 2/365 (0.5%) | 0/364 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Lenalidomide + Dexamethasone (Rd) | Daratumumab + Lenalidomide + Dexamethasone (DRd) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 355/365 (97.3%) | 362/364 (99.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 136/365 (37.3%) | 126/364 (34.6%) | ||
| Leukopenia | 34/365 (9.3%) | 68/364 (18.7%) | ||
| Lymphopenia | 45/365 (12.3%) | 66/364 (18.1%) | ||
| Neutropenia | 154/365 (42.2%) | 207/364 (56.9%) | ||
| Thrombocytopenia | 68/365 (18.6%) | 68/364 (18.7%) | ||
| Cardiac disorders | ||||
| Atrial Fibrillation | 29/365 (7.9%) | 19/364 (5.2%) | ||
| Eye disorders | ||||
| Cataract | 55/365 (15.1%) | 52/364 (14.3%) | ||
| Vision Blurred | 16/365 (4.4%) | 26/364 (7.1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 33/365 (9%) | 40/364 (11%) | ||
| Abdominal Pain Upper | 28/365 (7.7%) | 33/364 (9.1%) | ||
| Constipation | 129/365 (35.3%) | 148/364 (40.7%) | ||
| Diarrhoea | 166/365 (45.5%) | 204/364 (56%) | ||
| Dry Mouth | 19/365 (5.2%) | 12/364 (3.3%) | ||
| Dyspepsia | 27/365 (7.4%) | 26/364 (7.1%) | ||
| Nausea | 83/365 (22.7%) | 115/364 (31.6%) | ||
| Stomatitis | 13/365 (3.6%) | 22/364 (6%) | ||
| Vomiting | 43/365 (11.8%) | 60/364 (16.5%) | ||
| General disorders | ||||
| Asthenia | 85/365 (23.3%) | 116/364 (31.9%) | ||
| Chills | 6/365 (1.6%) | 45/364 (12.4%) | ||
| Fatigue | 104/365 (28.5%) | 145/364 (39.8%) | ||
| Oedema Peripheral | 107/365 (29.3%) | 140/364 (38.5%) | ||
| Peripheral Swelling | 19/365 (5.2%) | 10/364 (2.7%) | ||
| Pyrexia | 58/365 (15.9%) | 70/364 (19.2%) | ||
| Infections and infestations | ||||
| Bronchitis | 73/365 (20%) | 100/364 (27.5%) | ||
| Influenza | 15/365 (4.1%) | 23/364 (6.3%) | ||
| Nasopharyngitis | 11/365 (3%) | 26/364 (7.1%) | ||
| Oral Candidiasis | 19/365 (5.2%) | 15/364 (4.1%) | ||
| Pneumonia | 25/365 (6.8%) | 41/364 (11.3%) | ||
| Rhinitis | 21/365 (5.8%) | 29/364 (8%) | ||
| Sinusitis | 14/365 (3.8%) | 20/364 (5.5%) | ||
| Upper Respiratory Tract Infection | 50/365 (13.7%) | 81/364 (22.3%) | ||
| Urinary Tract Infection | 34/365 (9.3%) | 60/364 (16.5%) | ||
| Viral Upper Respiratory Tract Infection | 46/365 (12.6%) | 55/364 (15.1%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 22/365 (6%) | 27/364 (7.4%) | ||
| Investigations | ||||
| Blood Creatinine Increased | 13/365 (3.6%) | 24/364 (6.6%) | ||
| Weight Decreased | 63/365 (17.3%) | 101/364 (27.7%) | ||
| Weight Increased | 6/365 (1.6%) | 25/364 (6.9%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 54/365 (14.8%) | 78/364 (21.4%) | ||
| Dehydration | 16/365 (4.4%) | 19/364 (5.2%) | ||
| Hyperglycaemia | 28/365 (7.7%) | 50/364 (13.7%) | ||
| Hypocalcaemia | 31/365 (8.5%) | 49/364 (13.5%) | ||
| Hypokalaemia | 60/365 (16.4%) | 72/364 (19.8%) | ||
| Hypomagnesaemia | 29/365 (7.9%) | 18/364 (4.9%) | ||
| Hyponatraemia | 11/365 (3%) | 19/364 (5.2%) | ||
| Hypophosphataemia | 7/365 (1.9%) | 19/364 (5.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 63/365 (17.3%) | 69/364 (19%) | ||
| Back Pain | 93/365 (25.5%) | 114/364 (31.3%) | ||
| Bone Pain | 33/365 (9%) | 34/364 (9.3%) | ||
| Muscle Spasms | 79/365 (21.6%) | 106/364 (29.1%) | ||
| Muscular Weakness | 22/365 (6%) | 30/364 (8.2%) | ||
| Musculoskeletal Chest Pain | 41/365 (11.2%) | 27/364 (7.4%) | ||
| Musculoskeletal Pain | 40/365 (11%) | 49/364 (13.5%) | ||
| Myalgia | 25/365 (6.8%) | 25/364 (6.9%) | ||
| Neck Pain | 26/365 (7.1%) | 21/364 (5.8%) | ||
| Pain in Extremity | 50/365 (13.7%) | 59/364 (16.2%) | ||
| Nervous system disorders | ||||
| Dizziness | 57/365 (15.6%) | 69/364 (19%) | ||
| Dysgeusia | 35/365 (9.6%) | 40/364 (11%) | ||
| Headache | 39/365 (10.7%) | 68/364 (18.7%) | ||
| Paraesthesia | 30/365 (8.2%) | 58/364 (15.9%) | ||
| Peripheral Sensory Neuropathy | 54/365 (14.8%) | 87/364 (23.9%) | ||
| Tremor | 51/365 (14%) | 57/364 (15.7%) | ||
| Psychiatric disorders | ||||
| Anxiety | 34/365 (9.3%) | 32/364 (8.8%) | ||
| Confusional State | 19/365 (5.2%) | 22/364 (6%) | ||
| Depression | 32/365 (8.8%) | 29/364 (8%) | ||
| Insomnia | 107/365 (29.3%) | 109/364 (29.9%) | ||
| Renal and urinary disorders | ||||
| Acute Kidney Injury | 15/365 (4.1%) | 23/364 (6.3%) | ||
| Chronic Kidney Disease | 18/365 (4.9%) | 21/364 (5.8%) | ||
| Renal Impairment | 27/365 (7.4%) | 26/364 (7.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 59/365 (16.2%) | 100/364 (27.5%) | ||
| Dysphonia | 18/365 (4.9%) | 27/364 (7.4%) | ||
| Dyspnoea | 56/365 (15.3%) | 97/364 (26.6%) | ||
| Dyspnoea Exertional | 21/365 (5.8%) | 23/364 (6.3%) | ||
| Epistaxis | 20/365 (5.5%) | 17/364 (4.7%) | ||
| Oropharyngeal Pain | 9/365 (2.5%) | 24/364 (6.6%) | ||
| Rhinorrhoea | 11/365 (3%) | 25/364 (6.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dry Skin | 14/365 (3.8%) | 25/364 (6.9%) | ||
| Erythema | 18/365 (4.9%) | 23/364 (6.3%) | ||
| Hyperhidrosis | 5/365 (1.4%) | 19/364 (5.2%) | ||
| Pruritus | 29/365 (7.9%) | 32/364 (8.8%) | ||
| Rash | 43/365 (11.8%) | 57/364 (15.7%) | ||
| Rash Generalised | 23/365 (6.3%) | 16/364 (4.4%) | ||
| Rash Maculo-Papular | 9/365 (2.5%) | 20/364 (5.5%) | ||
| Vascular disorders | ||||
| Deep Vein Thrombosis | 27/365 (7.4%) | 26/364 (7.1%) | ||
| Hypertension | 26/365 (7.1%) | 46/364 (12.6%) | ||
| Hypotension | 32/365 (8.8%) | 34/364 (9.3%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
| Name/Title | Director |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | 844-434-4210 |
| ClinicalTrialDisclosure@its.jnj.com |
- CR104762
- 54767414MMY3008
- 2014-002273-11