Amyloidosis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of daratumumab plus cyclophosphamide, bortezomib and dexamethasone (CyBorD) compared with CyBorD alone in treatment of newly diagnosed amyloid light chain (AL) amyloidosis participants.
Detailed description
Participant involved in study for approx. 8 years duration includes Screening Phase (complete clinical evaluation will be done), Treatment Phase (monitoring of adverse events (AEs), laboratory abnormalities and clinical response), Post-Treatment Observation Phase (disease evaluations will be done) and a Long-term Follow-up Phase (Subsequent anticancer treatment, response to subsequent treatment, date of progression and survival status will be obtained every 16 weeks).The primary hypothesis is that daratumumab in combination with CyBorD will improve the overall complete hematological response rate compared to CyBorD alone in AL amyloidosis participants. Safety will be assessed by AEs, laboratory test results, electrocardiogram, vital sign measurements, physical examination, and Eastern Cooperative Oncology Group (ECOG) performance status.
Interventions
DRUGCyclophosphamide
Participants will receive 300 mg/m\^2 of cyclophosphamide as an oral or IV dose.
DRUGBortezomib
Participants will receive 1.3 mg/m\^2 of bortezomib as an subcutaneous (SC) injection.
DRUGDexamethasone, 40 mg
Participants of CyBorD alone arm will receive 40 mg dexamethasone orally or IV dose. Participants of CyBorD plus daratumumab arm will receive dexamethasone 20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing to make a total of 40 mg.
DRUGDaratumumab
Participants will receive 1800 mg of daratumumab subcutaneously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance * Measurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following: 1. serum monoclonal (M)-protein greater than or equal (\>=) 0.5 grams/deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation \[IFE\] performed at a central laboratory) 2. serum free light chain greater than or equal to (\>=) 50 milligram/Liter (mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) \>= 50 mg/L * One or more organs impacted by AL amyloidosis according to consensus guidelines * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
Exclusion criteria
* Prior therapy for AL amyloidosis or multiple myeloma including medications that target CD38, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to randomization * Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, \>= 60 percent (%) plasma cells in the bone marrow, or hypercalcemia * Evidence of significant cardiovascular conditions as specified below: 1. NT-ProBNP \> 8500 nanogram per liter (ng/L) 2. New York Heart Association (NYHA) classification IIIB or IV heart failure 3. Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram \[ECG\] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy 4. Inpatient admission to a hospital for unstable angina or myocardial infarction within the last 6 months prior to first dose or percutaneous cardiac intervention with recent stent within 6 months or coronary artery bypass grafting within 6 months 5. For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization 6. Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillators \[ICD\] is indicated but not placed (participants who do have a pacemaker/ICD are allowed on study) 7. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \> 500 milliseconds (msec). Participants who have a pacemaker may be included regardless of calculated QTc interval 8. Supine systolic blood pressure \< 90 millimeter of mercury (mmHg), or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of \> 20 mmHg despite medical management (eg, midodrine, fludrocortisones) in the absence of volume depletion * Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted * Known to be seropositive for human immunodeficiency virus (HIV) * Any one of the following: 1. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded 2. Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy) * Grade 2 sensory or Grade 1 painful peripheral neuropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Complete Hematologic Response (CHR) | Up to 2.4 years | Overall CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain (iFLC) is less than (\<) upper limit of normal (ULN) and serum and urine Immunofixation electrophoresis (IFE) are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for complete response (CR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of first randomization (Day -3) up to 7.1 years | Overall survival (OS) was measured from the date of randomization to the date of the participant's death. |
| Organ Response Rate (OrRR) at 6 Months: Cardiac Response | Month 6 | The Organ Response Rate (OrRR) for heart was defined as the percentage of participants with baseline involvement of the heart who achieved a confirmed organ response in the heart. Cardiac response was defined as as a decrease of \>30% in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and greater than (\>)300 nanogram/Litre (ng/L). |
| Organ Response Rate (OrRR) at 6 Months: Renal Response | Month 6 | The OrRR for kidney was defined as the percentage of participants with baseline involvement of the kidney who achieved a confirmed renal response in the kidney. Renal response was defined as more than equal to (≥) 30% decrease in proteinuria or proteinuria decreased to \<0.5 grams (g)/24 hours in the absence of renal progression. |
| Organ Response Rate (OrRR) at 6 Months: Liver Response | Month 6 | The OrRR for liver was defined as the percentage of participants with baseline involvement of the liver who achieved a confirmed liver response in the liver. Liver response was defined as 50% decrease in abnormal alkaline phosphatase value. |
| Percentage of Participants Who Achieved Complete Hematologic Response (CHR) at 6 Months | Month 6 | CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain is \< ULN and serum and urine IFE are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for Complete Response (CR). |
| Time to Complete Hematologic Response (CHR) | From date of first randomization (Day -3) up to 6.5 years | Time to CHR was defined as time between the date of randomization and first efficacy evaluation at which the participant has met all criteria for hematologic CR. CHR was primarily defined by negative immunofixation results and normalized free light chain (FLC) parameters. |
| Time to Cardiac Response | From date of first randomization (Day -3) up to 6.5 years | Time to cardiac response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had cardiac response. |
| Major Organ Deterioration Progression-Free Survival (MOD-PFS) | From date of first randomization (Day -3) upto 6.5 years | MOD-PFS was defined as duration from the date of randomization to either hematologic progression, or major organ deterioration (clinical manifestation of cardiac failure or renal failure), or death, whichever occurred first. Per international amyloidosis consensus criteria (IACC), hematologic progression was defined as satisfying any one of the following criteria: 1) From CHR, abnormal free light chain ratio (light chain must be double and \>ULN); 2) From CHR/VGPR/PR, 50 percent (%) increase in serum M-protein to \>0.5 grams per deciliter (g/dL) or 50% increase in urine M-protein to 200 milligrams (mg)/day; 3) free light chain increase of 50% to 100 milligrams (mg)/Liter (L). |
| Time to Renal Response | From date of first randomization (Day -3) up to 6.5 years | Time to renal response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had renal response. |
| Time to Subsequent Non-cross Resistant Anti-plasma Cell Therapy | From date of first randomization (Day -3) up to 6.5 years | Time to subsequent non-cross resistant anti-plasma cell therapy was defined as the time from the date of randomization to the start date of subsequent non-cross resistant, anti-plasma cell therapy. |
| Duration of Complete Hematologic Response (CHR) | From date of first randomization (Day -3) up to 6.5 years | Duration of CHR was defined as the time between the date of initial documentation of CHR to the date of first documented evidence of hematologic progressive diseased. CHR was primarily defined by negative immunofixation results and normalized FLC parameters. |
| Hematologic Very Good Partial Response (VGPR) or Better Rate | From date of first randomization (Day -3) up to 6.5 years | Hematologic VGPR or Better Rate was defined as percentage of participants who achieved hematologic Complete response (CR) or VGPR. VGPR was defined as the difference between involved iFLC and uFLC after treatment for baseline difference between iFLC and uFLC (dFLC) \>50 milligrams per liter (mg/L): Reduction in the dFLC \<40 mg/L. For Baseline dFLC \< 50 mg/L: more than (\>) 90% reduction in serum M-protein plus urine M-protein \<100 mg/24 hours. CR was negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \< 5% PCs in bone marrow. |
| Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Baseline (Day -28), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96 | The EORTC-QLQ-C30 a 30-question tool was used to assess the overall quality of life (QoL) in cancer patients. It included 30 items resulting in 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 Global health status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The 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 QoL. Scores were transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. |
| Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Baseline (Day -28), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96 | The SF-36 Health Survey was a generic measure of health status. The SF-36 consisted of 36 questions that yield an eight-scale (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) profile of functional health and well-being, as well as 2 physical and mental health summary measures and a preference-based health utility index. The physical component summary (PCS), the mental component summary (MCS), and the 8 domain scores range from zero (0) to 100, with higher scores representing higher level of functioning. |
| Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Baseline (Day -28), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96 | The EORTC-QLQ-C30 a 30-question tool was used to assess the overall QoL in cancer patients. It included 30 items resulting in 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 GHS scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The 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 QoL. Scores were transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. |
| Time to Liver Response | From date of first randomization (Day -3) up to 6.5 years | Time to liver response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had liver response. |
Countries
Australia, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Poland, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Participants with newly diagnosed Amyloid Light-chain (AL) amyloidosis with measurable disease and at least one organ involvement, and Mayo cardiac stage I - IIIA, who had not received prior therapy for AL amyloidosis or multiple myeloma were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Run-In: Daratumumab Plus CyBorD Participants received the combination therapy during Run-in phase starting with 20 milligrams (mg) dexamethasone as premedication followed by daratumumab 1800 mg on Day 1 Cycle 1, then cyclophosphamide 300 milligram per meter square (mg/m\^2) orally or intravenous (IV) maximum weekly dose 500 mg, followed by bortezomib 1.3 mg/m\^2 subcutaneous (SC) injection once every week and dexamethasone remaining 20 mg post daratumumab dosing for up to 1 cycle (28 Days) to assess the safety before randomizing participants in CyBorD or daratumumab plus CyBorD arms. However, participants also continued daratumumab plus CyBorD for up to 6 cycles and then daratumumab monotherapy for up to 24 months from the start of treatment. After completion of treatment phase participants entered into the post treatment observation phase and were continued with disease evaluations every 8 weeks post last dose up to disease progression (up to 6.5 years). Participants then entered into long term follow up phase and were followed up for survival every 16 weeks (up to 7.1 years). | 28 |
| CyBorD Participants received dexamethasone (40 mg weekly dose)starting from cycle 1 day1 in every 28-day cycle followed by cyclophosphamide 300 mg/m\^2 orally or IV maximum weekly dose 500 mg and then bortezomib 1.3 mg/m\^2 SC injection once weekly up to 7.33 months. All cycles were of 28 days. After completion of treatment phase participants entered into the post treatment observation phase and were continued with disease evaluations every 8 weeks post last dose up to disease progression (up to 6.5 years). Participants then entered into long term follow up phase and were followed up for survival every 16 weeks (up to 7.1 years). | 193 |
| Daratumumab Plus CyBorD Participants received combination therapy for six cycles of 28 days each, daratumumab 1800 mg SC weekly starting from cycles 1 day 1 and cycle 2, every 2 weeks in cycles 3 through 6, dexamethasone 40 mg weekly (on days of daratumumab dosing, dexamethasone was split, 20 mg as premedication and 20 mg as post daratumumab dosing), cyclophosphamide 300 mg/m\^2 orally or IV maximum weekly dose 500 mg, bortezomib 1.3 mg/m\^2 SC injection once weekly. After 6 cycles, participants continued to receive daratumumab SC monotherapy until disease progression, start of subsequent therapy or up to 26.71 months from the first dose of study treatment. All cycles were of 28 days. After completion of treatment phase participants entered into the post treatment observation phase and were continued with disease evaluations every 8 weeks post last dose up to disease progression (up to 6.5 years). Participants then entered into long term follow up phase and were followed up for survival every 16 weeks (up to 7.1 years). | 195 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 5 | 65 | 47 |
| Overall Study | Lost to Follow-up | 0 | 6 | 0 |
| Overall Study | Sponsor's Decision | 20 | 99 | 140 |
| Overall Study | Withdrawal by Subject | 3 | 23 | 8 |
Baseline characteristics
| Characteristic | CyBorD | Total | Run-In: Daratumumab Plus CyBorD | Daratumumab Plus CyBorD |
|---|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 9.66 | 63.2 years STANDARD_DEVIATION 10.03 | 64.8 years STANDARD_DEVIATION 11.2 | 62.2 years STANDARD_DEVIATION 10.16 |
| Baseline Major Organ Involvement Baseline Organ Involvement: Heart | 137 Participants | 294 Participants | 17 Participants | 140 Participants |
| Baseline Major Organ Involvement Baseline Organ Involvement: Kidney | 114 Participants | 248 Participants | 19 Participants | 115 Participants |
| Baseline Major Organ Involvement Baseline Organ Involvement: Liver | 16 Participants | 35 Participants | 4 Participants | 15 Participants |
| Cardiac Stage Based on Mayo Clinic Cardiac Staging System Class I | 43 Participants | 96 Participants | 6 Participants | 47 Participants |
| Cardiac Stage Based on Mayo Clinic Cardiac Staging System Class II | 80 Participants | 172 Participants | 16 Participants | 76 Participants |
| Cardiac Stage Based on Mayo Clinic Cardiac Staging System Class IIIa | 64 Participants | 139 Participants | 5 Participants | 70 Participants |
| Cardiac Stage Based on Mayo Clinic Cardiac Staging System Class IIIb | 6 Participants | 9 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 23 Participants | 1 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 176 Participants | 381 Participants | 26 Participants | 179 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 12 Participants | 1 Participants | 7 Participants |
| New York Heart Association (NYHA) Class Class I | 94 Participants | 212 Participants | 17 Participants | 101 Participants |
| New York Heart Association (NYHA) Class Class II | 89 Participants | 176 Participants | 10 Participants | 77 Participants |
| New York Heart Association (NYHA) Class Class IIIA | 10 Participants | 28 Participants | 1 Participants | 17 Participants |
| Number of Organs Involved 1 Organ | 68 Participants | 143 Participants | 9 Participants | 66 Participants |
| Number of Organs Involved 2 Organs | 77 Participants | 166 Participants | 13 Participants | 76 Participants |
| Number of Organs Involved >=3 Organ | 48 Participants | 107 Participants | 6 Participants | 53 Participants |
| Number of Organs Involved | 2.0 organs STANDARD_DEVIATION 1.03 | 2.0 organs STANDARD_DEVIATION 0.99 | 2.0 organs STANDARD_DEVIATION 0.881 | 2.0 organs STANDARD_DEVIATION 0.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 34 Participants | 64 Participants | 0 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 15 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 13 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) White | 143 Participants | 319 Participants | 25 Participants | 151 Participants |
| Region of Enrollment AUSTRALIA | 15 Participants | 27 Participants | 0 Participants | 12 Participants |
| Region of Enrollment BELGIUM | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Region of Enrollment BRAZIL | 7 Participants | 11 Participants | 0 Participants | 4 Participants |
| Region of Enrollment CANADA | 10 Participants | 19 Participants | 0 Participants | 9 Participants |
| Region of Enrollment CHINA | 6 Participants | 12 Participants | 0 Participants | 6 Participants |
| Region of Enrollment DENMARK | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Region of Enrollment FRANCE | 22 Participants | 38 Participants | 0 Participants | 16 Participants |
| Region of Enrollment GERMANY | 11 Participants | 19 Participants | 0 Participants | 8 Participants |
| Region of Enrollment GREECE | 11 Participants | 27 Participants | 0 Participants | 16 Participants |
| Region of Enrollment HUNGARY | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Region of Enrollment ISRAEL | 5 Participants | 11 Participants | 0 Participants | 6 Participants |
| Region of Enrollment ITALY | 5 Participants | 9 Participants | 0 Participants | 4 Participants |
| Region of Enrollment JAPAN | 13 Participants | 28 Participants | 0 Participants | 15 Participants |
| Region of Enrollment MEXICO | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Region of Enrollment NETHERLANDS | 4 Participants | 11 Participants | 0 Participants | 7 Participants |
| Region of Enrollment POLAND | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Region of Enrollment SOUTH KOREA | 12 Participants | 20 Participants | 0 Participants | 8 Participants |
| Region of Enrollment SPAIN | 11 Participants | 32 Participants | 0 Participants | 21 Participants |
| Region of Enrollment SWEDEN | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Region of Enrollment TURKEY | 7 Participants | 17 Participants | 0 Participants | 10 Participants |
| Region of Enrollment UNITED KINGDOM | 4 Participants | 8 Participants | 0 Participants | 4 Participants |
| Region of Enrollment UNITED STATES | 41 Participants | 109 Participants | 28 Participants | 40 Participants |
| Sex/Gender, Customized Female | 76 Participants | 174 Participants | 11 Participants | 87 Participants |
| Sex/Gender, Customized Male | 117 Participants | 241 Participants | 16 Participants | 108 Participants |
| Sex/Gender, Customized Undifferentiated Sex | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Weight group in Kilograms (Kg) <=65 kg | 74 Participants | 141 Participants | 5 Participants | 62 Participants |
| Weight group in Kilograms (Kg) >65 to 85 kg | 74 Participants | 182 Participants | 12 Participants | 96 Participants |
| Weight group in Kilograms (Kg) >85 kg | 45 Participants | 93 Participants | 11 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 28 | 67 / 193 | 47 / 195 |
| other Total, other adverse events | 27 / 28 | 181 / 188 | 184 / 193 |
| serious Total, serious adverse events | 12 / 28 | 68 / 188 | 91 / 193 |
Outcome results
Primary
Percentage of Participants With Overall Complete Hematologic Response (CHR)
Overall CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain (iFLC) is less than (\<) upper limit of normal (ULN) and serum and urine Immunofixation electrophoresis (IFE) are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for complete response (CR).
Time frame: Up to 2.4 years
Population: The intent to treat analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Data for this outcome measure (OM) was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CyBorD | Percentage of Participants With Overall Complete Hematologic Response (CHR) | 18.1 percentage of participants |
| Daratumumab Plus CyBorD | Percentage of Participants With Overall Complete Hematologic Response (CHR) | 53.3 percentage of participants |
p-value: <0.000195% CI: [3.22, 8.16]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in EORTC QLQ-C30 Global Health Status Score
The EORTC-QLQ-C30 a 30-question tool was used to assess the overall QoL in cancer patients. It included 30 items resulting in 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 GHS scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The 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 QoL. Scores were transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms.
Time frame: Baseline (Day -28), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96
Population: The intent to treat analysis set included all randomized participants. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 36 | 2.97 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 68 | 6.19 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 40 | -6.13 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 12 | -6.00 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 48 | -0.71 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 52 | -0.17 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 20 | -5.46 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 56 | 3.62 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 60 | 2.33 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 28 | -3.81 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 64 | -5.49 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 92 | 3.18 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 72 | -4.26 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 76 | 2.00 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 24 | -4.26 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 80 | 4.13 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 4 | -3.02 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 84 | 3.69 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 44 | -1.37 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 88 | -2.95 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 32 | 3.03 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 8 | -4.15 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 96 | 6.54 Score on scale |
| CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 16 | -7.17 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 96 | 8.03 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 44 | 0.16 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 48 | 6.79 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 56 | 4.02 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 68 | 4.95 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 72 | 8.94 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 4 | -2.72 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 8 | -3.83 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 12 | -1.70 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 16 | -2.75 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 20 | -2.53 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 24 | -0.76 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 28 | -1.96 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 32 | 1.36 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 36 | 3.09 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 40 | 5.10 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 52 | 8.61 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 60 | 5.85 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 64 | 8.27 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 76 | 10.34 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 80 | 7.05 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 84 | 6.85 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 88 | 7.59 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Week 92 | 8.08 Score on scale |
Secondary
Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue
The EORTC-QLQ-C30 a 30-question tool was used to assess the overall quality of life (QoL) in cancer patients. It included 30 items resulting in 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 Global health status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The 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 QoL. Scores were transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms.
Time frame: Baseline (Day -28), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96
Population: The intent to treat analysis set included all randomized participants. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 52 | -1.69 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 28 | 3.30 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 56 | -1.88 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 8 | 4.04 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 60 | -2.62 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 24 | 0.69 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 64 | -3.55 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 12 | 6.35 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 68 | 0.84 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 32 | -3.14 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 72 | -0.44 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 16 | 9.92 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 76 | -5.08 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 36 | -10.25 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 80 | -6.00 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 20 | 6.83 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 84 | -17.23 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 44 | 1.57 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 88 | -6.71 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 40 | 2.09 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 92 | -7.43 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 48 | -2.82 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 96 | -5.75 Score on scale |
| CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 4 | 3.79 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 96 | -8.56 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 20 | 3.87 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 24 | 0.30 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 28 | 2.14 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 36 | -12.59 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 4 | 2.07 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 8 | 3.93 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 12 | 2.77 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 16 | 1.54 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 40 | -5.39 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 44 | -9.55 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 48 | -7.99 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 52 | -5.56 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 56 | -6.77 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 60 | -9.23 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 64 | -10.36 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 68 | -5.96 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 72 | -11.80 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 76 | -8.91 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 80 | -10.79 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 84 | -10.39 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 88 | -9.83 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 92 | -12.11 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Fatigue | Week 32 | -4.92 Score on scale |
Secondary
Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS)
The SF-36 Health Survey was a generic measure of health status. The SF-36 consisted of 36 questions that yield an eight-scale (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) profile of functional health and well-being, as well as 2 physical and mental health summary measures and a preference-based health utility index. The physical component summary (PCS), the mental component summary (MCS), and the 8 domain scores range from zero (0) to 100, with higher scores representing higher level of functioning.
Time frame: Baseline (Day -28), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96
Population: The intent to treat analysis set included all randomized participants. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 80 | 0.47 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 44 | 1.30 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 4 | -0.43 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 48 | 0.26 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 24 | -1.84 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 52 | 0.69 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 12 | -1.86 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 60 | 2.20 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 56 | -0.35 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 68 | 0.68 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 16 | -3.15 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 72 | -1.21 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 28 | -3.26 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 76 | 1.05 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 20 | -2.36 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 8 | -1.09 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 84 | 3.21 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 32 | 0.19 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 88 | 2.12 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 36 | -0.45 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 92 | -2.50 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 64 | -2.00 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 96 | -0.03 Score on scale |
| CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 40 | -0.56 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 96 | 2.96 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 20 | -0.42 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 28 | -0.93 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 32 | 0.61 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 56 | 0.91 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 60 | 1.32 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 8 | -1.42 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 12 | -0.17 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 16 | -0.35 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 24 | -0.60 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 36 | 1.22 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 40 | 2.02 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 44 | 1.55 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 48 | 2.18 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 52 | 1.33 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 64 | 2.74 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 68 | 1.25 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 72 | 2.03 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 76 | 0.12 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 80 | 2.32 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 84 | 1.56 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 88 | 2.57 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 92 | 1.31 Score on scale |
| Daratumumab Plus CyBorD | Change From Baseline in the Short Form Health Survey, Version 2, the Mental Component Summary, (SF-36v2 MCS) | Week 4 | -0.19 Score on scale |
Secondary
Duration of Complete Hematologic Response (CHR)
Duration of CHR was defined as the time between the date of initial documentation of CHR to the date of first documented evidence of hematologic progressive diseased. CHR was primarily defined by negative immunofixation results and normalized FLC parameters.
Time frame: From date of first randomization (Day -3) up to 6.5 years
Population: Responders in intent-to-treat analysis set included all randomized participants. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Duration of Complete Hematologic Response (CHR) | NA Months |
| Daratumumab Plus CyBorD | Duration of Complete Hematologic Response (CHR) | NA Months |
Secondary
Hematologic Very Good Partial Response (VGPR) or Better Rate
Hematologic VGPR or Better Rate was defined as percentage of participants who achieved hematologic Complete response (CR) or VGPR. VGPR was defined as the difference between involved iFLC and uFLC after treatment for baseline difference between iFLC and uFLC (dFLC) \>50 milligrams per liter (mg/L): Reduction in the dFLC \<40 mg/L. For Baseline dFLC \< 50 mg/L: more than (\>) 90% reduction in serum M-protein plus urine M-protein \<100 mg/24 hours. CR was negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \< 5% PCs in bone marrow.
Time frame: From date of first randomization (Day -3) up to 6.5 years
Population: The intent to treat analysis set included all randomized participants. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CyBorD | Hematologic Very Good Partial Response (VGPR) or Better Rate | 50.3 Percentage of participants |
| Daratumumab Plus CyBorD | Hematologic Very Good Partial Response (VGPR) or Better Rate | 79.0 Percentage of participants |
Secondary
Major Organ Deterioration Progression-Free Survival (MOD-PFS)
MOD-PFS was defined as duration from the date of randomization to either hematologic progression, or major organ deterioration (clinical manifestation of cardiac failure or renal failure), or death, whichever occurred first. Per international amyloidosis consensus criteria (IACC), hematologic progression was defined as satisfying any one of the following criteria: 1) From CHR, abnormal free light chain ratio (light chain must be double and \>ULN); 2) From CHR/VGPR/PR, 50 percent (%) increase in serum M-protein to \>0.5 grams per deciliter (g/dL) or 50% increase in urine M-protein to 200 milligrams (mg)/day; 3) free light chain increase of 50% to 100 milligrams (mg)/Liter (L).
Time frame: From date of first randomization (Day -3) upto 6.5 years
Population: The intent to treat analysis set included all randomized participants. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Major Organ Deterioration Progression-Free Survival (MOD-PFS) | 30.23 months |
| Daratumumab Plus CyBorD | Major Organ Deterioration Progression-Free Survival (MOD-PFS) | NA months |
Secondary
Organ Response Rate (OrRR) at 6 Months: Cardiac Response
The Organ Response Rate (OrRR) for heart was defined as the percentage of participants with baseline involvement of the heart who achieved a confirmed organ response in the heart. Cardiac response was defined as as a decrease of \>30% in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and greater than (\>)300 nanogram/Litre (ng/L).
Time frame: Month 6
Population: Cardiac response-evaluable participants had baseline NT-proBNP \>=650 ng/L or NYHA class 3 or 4, plus received at least 1 administration of study treatment and had at least one post-baseline. NT-proBNP measurement (if baseline NT-proBNP \>=650 nanograms per liter \[ng/L\]) or NYHA function evaluation (if baseline NYHA class 3 or 4). Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CyBorD | Organ Response Rate (OrRR) at 6 Months: Cardiac Response | 22.2 Percentage of participants |
| Daratumumab Plus CyBorD | Organ Response Rate (OrRR) at 6 Months: Cardiac Response | 41.5 Percentage of participants |
Secondary
Organ Response Rate (OrRR) at 6 Months: Liver Response
The OrRR for liver was defined as the percentage of participants with baseline involvement of the liver who achieved a confirmed liver response in the liver. Liver response was defined as 50% decrease in abnormal alkaline phosphatase value.
Time frame: Month 6
Population: Liver response-evaluable participants had baseline abnormal alkaline phosphatase \>1.5\*upper limit of normal (ULN), at least 1 administration of study treatment and had at least one post-baseline alkaline phosphatase measurement. Data for this outcome measure was planned to be collected and analyzed for specified arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CyBorD | Organ Response Rate (OrRR) at 6 Months: Liver Response | 7.1 Percentage of participants |
| Daratumumab Plus CyBorD | Organ Response Rate (OrRR) at 6 Months: Liver Response | 40.0 Percentage of participants |
Secondary
Organ Response Rate (OrRR) at 6 Months: Renal Response
The OrRR for kidney was defined as the percentage of participants with baseline involvement of the kidney who achieved a confirmed renal response in the kidney. Renal response was defined as more than equal to (≥) 30% decrease in proteinuria or proteinuria decreased to \<0.5 grams (g)/24 hours in the absence of renal progression.
Time frame: Month 6
Population: Renal response-evaluable participants had baseline urine protein \>0.5 g/day, received at least one administration of study treatment, and had at least post-baseline urine protein measurement. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CyBorD | Organ Response Rate (OrRR) at 6 Months: Renal Response | 27.4 Percentage of participants |
| Daratumumab Plus CyBorD | Organ Response Rate (OrRR) at 6 Months: Renal Response | 53.8 Percentage of participants |
Secondary
Overall Survival (OS)
Overall survival (OS) was measured from the date of randomization to the date of the participant's death.
Time frame: From date of first randomization (Day -3) up to 7.1 years
Population: The intent to treat analysis set included all randomized participants. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Overall Survival (OS) | NA Months |
| Daratumumab Plus CyBorD | Overall Survival (OS) | NA Months |
Secondary
Percentage of Participants Who Achieved Complete Hematologic Response (CHR) at 6 Months
CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain is \< ULN and serum and urine IFE are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for Complete Response (CR).
Time frame: Month 6
Population: The intent to treat analysis set included all randomized participants. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CyBorD | Percentage of Participants Who Achieved Complete Hematologic Response (CHR) at 6 Months | 14.0 Percentage of participants |
| Daratumumab Plus CyBorD | Percentage of Participants Who Achieved Complete Hematologic Response (CHR) at 6 Months | 50.3 Percentage of participants |
Secondary
Time to Cardiac Response
Time to cardiac response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had cardiac response.
Time frame: From date of first randomization (Day -3) up to 6.5 years
Population: Cardiac response-evaluable participants had baseline NT-proBNP greater than equal to \>= 650 ng/L or NYHA class 3/4, with at least one post-baseline NT-proBNP or NYHA assessment after receiving treatment. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for specified arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Time to Cardiac Response | 4.67 Months |
| Daratumumab Plus CyBorD | Time to Cardiac Response | 3.84 Months |
Secondary
Time to Complete Hematologic Response (CHR)
Time to CHR was defined as time between the date of randomization and first efficacy evaluation at which the participant has met all criteria for hematologic CR. CHR was primarily defined by negative immunofixation results and normalized free light chain (FLC) parameters.
Time frame: From date of first randomization (Day -3) up to 6.5 years
Population: Responders in intent to-treat analysis set included participants of intent to-treat analysis set who had hematologic response (complete hematologic response, VGPR and PR). Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Time to Complete Hematologic Response (CHR) | 85.00 Days |
| Daratumumab Plus CyBorD | Time to Complete Hematologic Response (CHR) | 67.50 Days |
Secondary
Time to Liver Response
Time to liver response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had liver response.
Time frame: From date of first randomization (Day -3) up to 6.5 years
Population: Liver response-evaluable participant had alkaline phosphatase \>1.5\*ULN, received treatment, and had a post-baseline test. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Time to Liver Response | 10.61 Months |
| Daratumumab Plus CyBorD | Time to Liver Response | 4.68 Months |
Secondary
Time to Renal Response
Time to renal response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had renal response.
Time frame: From date of first randomization (Day -3) up to 6.5 years
Population: Renal response-evaluable participants had urine protein \>0.5 g/day at baseline, received treatment, and had a postbaseline urine test. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Time to Renal Response | 3.75 Months |
| Daratumumab Plus CyBorD | Time to Renal Response | 1.91 Months |
Secondary
Time to Subsequent Non-cross Resistant Anti-plasma Cell Therapy
Time to subsequent non-cross resistant anti-plasma cell therapy was defined as the time from the date of randomization to the start date of subsequent non-cross resistant, anti-plasma cell therapy.
Time frame: From date of first randomization (Day -3) up to 6.5 years
Population: The intent to treat analysis set included all randomized participants. Data for this outcome measure was planned to be collected and analyzed for specified arms only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CyBorD | Time to Subsequent Non-cross Resistant Anti-plasma Cell Therapy | 11.30 Months |
| Daratumumab Plus CyBorD | Time to Subsequent Non-cross Resistant Anti-plasma Cell Therapy | NA Months |