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| ID | Type | Description | Link |
|---|---|---|---|
| 54767414AMY3001 | Other Identifier | Janssen Research & Development, LLC | |
| 2016-001737-27 | EudraCT Number | ||
| 2024-511967-26-00 | Registry Identifier | EUCT number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CyBorD alone (cyclophosphamide/bortezomib/dexamethasone) | Active Comparator | Participants will receive dexamethasone (40 milligrams [mg] orally or intravenous [IV] dose), followed by cyclophosphamide (300 milligram per meter square [mg/m^2] orally or IV dose), then bortezomib (1.3 mg/m^2 subcutaneous injection) weekly on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. |
|
| CyBorD plus Daratumumab | Experimental | Participants will receive dexamethasone (20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing) followed by 1800 mg of daratumumab subcutaneously followed by cyclophosphamide (300 mg/m^2 orally or IV dose weekly) and bortezomib (1.3 mg/m^2 subcutaneous injection weekly) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 2 years. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | Participants will receive 300 mg/m^2 of cyclophosphamide as an oral or IV dose. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Up to 2.4 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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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:
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:
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:
Grade 2 sensory or Grade 1 painful peripheral neuropathy
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic Arizona | Phoenix | Arizona | 85054 | United States | ||
| City of Hope |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42118698 | Derived | Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Mollee P, Lu J, Schonland SO, Gatt ME, Suzuki K, Kim K, Cibeira MT, Bhutani M, Beksac M, Libby EN, Valent J, Hungria V, Rosenzweig MA, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman A, Goodman S, Zonder JA, Lam S, Song KW, Hansen T, Manier S, Roeloffzen WWH, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe EQ, Tran N, Wang J, Chen Y, Vasey SY, Schecter JM, Vermeulen J, Comenzo R, Merlini G. Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone in Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis. Blood. 2026 May 12:blood.2025032099. doi: 10.1182/blood.2025032099. Online ahead of print. | |
| 36862168 |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 10, 2019 | Feb 11, 2021 |
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| Bortezomib | Drug | Participants will receive 1.3 mg/m^2 of bortezomib as an subcutaneous (SC) injection. |
|
| Dexamethasone, 40 mg | Drug | 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. |
|
| Daratumumab | Drug | Participants will receive 1800 mg of daratumumab subcutaneously. |
|
| From date of first randomization (Day -3) upto 6.5 years |
| Overall Survival (OS) | Overall survival (OS) was measured from the date of randomization to the date of the participant's death. | From date of first randomization (Day -3) up to 7.1 years |
| 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). | Month 6 |
| 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. | Month 6 |
| 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. | Month 6 |
| 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). | Month 6 |
| 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. | From date of first randomization (Day -3) up to 6.5 years |
| 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. | From date of first randomization (Day -3) up to 6.5 years |
| 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. | From date of first randomization (Day -3) up to 6.5 years |
| 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. | From date of first randomization (Day -3) up to 6.5 years |
| 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. | From date of first randomization (Day -3) up to 6.5 years |
| 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. | From date of first randomization (Day -3) up to 6.5 years |
| 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. | From date of first randomization (Day -3) up to 6.5 years |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| Duarte |
| California |
| 91010 |
| United States |
| University of California San Francisco | San Francisco | California | 94143 | United States |
| Stanford University | Stanford | California | 94305 | United States |
| University of Colorado | Aurora | Colorado | 80045 | United States |
| Colorado Blood Cancer Institute | Denver | Colorado | 80218 | United States |
| Mayo Clinic | Jacksonville | Florida | 32224 | United States |
| Winship Cancer Institute Emory University | Atlanta | Georgia | 30322 | United States |
| University of Maryland | Baltimore | Maryland | 21201 | United States |
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
| Boston University Medical Center | Boston | Massachusetts | 02118 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215-5418 | United States |
| Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Mayo Clinic Rochester | Rochester | Minnesota | 55905 | United States |
| Washington University School Of Medicine | St Louis | Missouri | 63110 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Weill Cornell Medical College | New York | New York | 10065 | United States |
| University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| Levine Cancer Institute | Charlotte | North Carolina | 28204 | United States |
| Wake Forest University Health Sciences - Cardiovascular Medicine | Winston-Salem | North Carolina | 27157 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| The Ohio State University | Columbus | Ohio | 43210 | United States |
| Oregon Health And Science University | Portland | Oregon | 97239 | United States |
| University of Pennsylvania Medical Center | Philadelphia | Pennsylvania | 19104 | United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| University of Texas, MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Huntsman Cancer Institute | Salt Lake City | Utah | 84112 | United States |
| Seattle Cancer Care Alliance | Seattle | Washington | 98109-1023 | United States |
| Box Hill Hospital | Box Hill | 3128 | Australia |
| Sir Charles Gairdner Hospital | Nedlands | 6009 | Australia |
| Westmead Hospital | Westmead | 2145 | Australia |
| Princess Alexandra Hospital | Woolloongabba | 4102 | Australia |
| Institut Jules Bordet | Anderlecht | 1070 | Belgium |
| UZ Gent | Ghent | 9000 | Belgium |
| Az Groeninge | Kortrijk | 8500 | Belgium |
| Universitair Ziekenhuis Leuven | Leuven | 3000 | Belgium |
| Hospital das Clinicas de Porto Alegre | Porto Alegre | 90035-903 | Brazil |
| Sociedade Pernambucana de Combate ao Cancer | Recife | 50040-000 | Brazil |
| Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI) | Rio de Janeiro | 22775 001 | Brazil |
| Hospital Sao Rafael | Salvador | 41253 190 | Brazil |
| Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base | São José do Rio Preto | 15090-000 | Brazil |
| Clinica Sao Germano | São Paulo | 01455 010 | Brazil |
| Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE | São Paulo | 04039-004 | Brazil |
| Hospital Das Clinicas Da Faculdade De Medicina Da USP | São Paulo | 05403-010 | Brazil |
| Arthur J E Child Comprehensive Cancer Centre | Calgary | Alberta | T2N 5G2 | Canada |
| Alberta Health Services | Edmonton | Alberta | T6G 1Z2 | Canada |
| Vancouver General Hospital | Vancouver | British Columbia | V5Z 1M9 | Canada |
| London Health Sciences Center | London | Ontario | N6A 5W9 | Canada |
| University Health Network UHN Princess Margaret Cancer Centre | Toronto | Ontario | M5G 2M9 | Canada |
| McGill University Health Centre | Montreal | Quebec | H4A 3J1 | Canada |
| Peking University First Hospital | Beijing | 100034 | China |
| Peking University People s Hospital | Beijing | 100044 | China |
| First affiliated Hospital of Zhejiang University | Hangzhou | 310020 | China |
| Ruijin Hospital Shanghai Jiao Tong University | Shanghai | 200025 | China |
| The First Affiliated Hospital of Wenzhou Medical University | Wenzhou | 325000 | China |
| Aarhus University Hospital | Aarhus N | DK-8200 | Denmark |
| Dep. of Hematology, Rigshospitalet | Copenhagen | 2400 | Denmark |
| Odense Universitets Hospital | Odense | 5000 | Denmark |
| CHU Dijon | Dijon | 21000 | France |
| Hopital Claude Huriez | Lille | 59037 | France |
| CHU de Limoges - Fédération Hépatologie | Limoges | 87000 | France |
| Institut Paoli Calmettes | Marseille | 13273 | France |
| Chu Hotel Dieu | Nantes | 44035 | France |
| Hopital Saint Louis | Paris | 75475 | France |
| Centre hospitalier Lyon-Sud | Pierre-Bénite | 69495 | France |
| CHU De Poitiers | Poitiers | 86000 | France |
| CHU Rangueil | Toulouse | 31400 | France |
| CHU Bretonneau | Tours | 37044 | France |
| CHU de Nancy_ Hopital Brabois | Vandœuvre-lès-Nancy | 54511 | France |
| Charite Campus Benjamin Franklin | Berlin | 12203 | Germany |
| Heinrich-Heine-Universität Düsseldorf | Düsseldorf | 40225 | Germany |
| Universitatsklinikum Essen | Essen | 45122 | Germany |
| HOPA-Hämatologisch-Onkologische Praxis Altona MVZ GmbH | Hamburg | 22767 | Germany |
| Universitaetsklinikum Heidelberg Medizinische Klinik V | Heidelberg | 69120 | Germany |
| Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II, | Tübingen | 72076 | Germany |
| Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii | Würzburg | 97080 | Germany |
| Alexandra General Hospital of Athens | Athens | 11528 | Greece |
| University General Hospital of Rio | Pátrai | 26500 | Greece |
| Semmelweis Egyetem I.Belgyogyaszati Klinika | Budapest | 1083 | Hungary |
| Semmelweis Egyetem I.Belgyogyaszati Klinika | Budapest | 1088 | Hungary |
| Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely | Budapest | 1097 | Hungary |
| Carmel Hospital | Haifa | 34362 | Israel |
| Hadassah Medical Center | Jerusalem | 91120 | Israel |
| Sheba Medical Center | Ramat Gan | 52621 | Israel |
| Sourasky Medical Center | Tel Aviv | 6423906 | Israel |
| Assaf Ha'Rofeh Medical Center | Ẕerifin | 70300 | Israel |
| Policlinico di Bari | Bari | 70124 | Italy |
| Istituto di Ematologia Serà gnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi | Bologna | 40138 | Italy |
| Casa di Cura La Maddalena | Palermo | 90146 | Italy |
| Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo | Pavia | 27100 | Italy |
| Dipartimento Di Biotecnologie Cellulari Ed Ematologia-Università ''La Sapienza'',Policlinico Umberto I | Roma | 00161 | Italy |
| A.O.U. Città della Salute e della Scienza | Torino | 10126 | Italy |
| Fukushima Medical University Hospital | Fukushima | 960 1295 | Japan |
| Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital | Hiroshima | 730-8619 | Japan |
| Teine Keijinkai Hospital | Hokkaido | 006-8555 | Japan |
| Kanazawa University Hospital | Kanazawa | 920 8641 | Japan |
| Kumamoto University Hospital | Kumamoto | 860-8556 | Japan |
| Kyoto Kuramaguchi Medical Center | Kyoto | 603-8151 | Japan |
| Shinshu University Hospital | Matsumoto | 390 8621 | Japan |
| Matsuyama Red Cross Hospital | Matsuyama | 790-8524 | Japan |
| Nagoya City University Hospital | Nagoya | 467 8602 | Japan |
| National Hospital Organization Okayama Medical Center | Okayama | 701-1192 | Japan |
| Japanese Red Cross Medical Center | Shibuya City | 150-8935 | Japan |
| Tokushima University Hospital | Tokushima | 770-8503 | Japan |
| Centro de Investigación Farmacéutica Especializada | Guadalajara | 44160 | Mexico |
| Hospital Universitario Dr Jose Eleuterio Gonzalez | Monterrey | 64460 | Mexico |
| UMCG | Groningen | 9713 GZ | Netherlands |
| Erasmus MC | Rotterdam | 3015 CN | Netherlands |
| Haga ziekenhuis | The Hague | 2545 AA | Netherlands |
| UMC Utrecht | Utrecht | 3584 CX | Netherlands |
| Maxima Medisch Centrum | Veldhoven | 5504 DB | Netherlands |
| Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich | Chorzów | 41-500 | Poland |
| SKPP UM w Poznaniu | Poznan | 60-569 | Poland |
| Instytut Hematologii i Transfuzjologii | Warsaw | 02 776 | Poland |
| Pusan National University Hospital | Busan | 49241 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Severance Hospital Yonsei University Health System | Seoul | 03722 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| The Catholic University of Korea Seoul St Marys Hospital | Seoul | 06591 | South Korea |
| Inst. Cat. D'Oncologia-Badalona | Badalona | 08916 | Spain |
| Hosp Univ Vall D Hebron | Barcelona | 08035 | Spain |
| Hosp Clinic de Barcelona | Barcelona | 08036 | Spain |
| Hosp. Univ. Ramon Y Cajal | Madrid | 28034 | Spain |
| Hosp Univ Fund Jimenez Diaz | Madrid | 28040 | Spain |
| Hosp. Univ. 12 de Octubre | Madrid | 28041 | Spain |
| Clinica Univ. de Navarra | Pamplona | 31008 | Spain |
| Hosp Clinico Univ de Salamanca | Salamanca | 37007 | Spain |
| Hosp. Univ. de Canarias | San Cristóbal de La Laguna | 38320 | Spain |
| Hosp. Univ. Dr. Peset | Valencia | 46017 | Spain |
| South Elvsborg Hospital | Borås | 501 82 | Sweden |
| Skanes universitetssjukhus | Lund | 221 85 | Sweden |
| Ankara Universitesi Tip Fakultesi Cebeci Hastanesi | Ankara | 06590 | Turkey (Türkiye) |
| Akdeniz University Medical Faculty | Antalya | 7059 | Turkey (Türkiye) |
| Ondokuz Mayis Universitesi Tip Fakultesiy | Atakum | 55270 | Turkey (Türkiye) |
| Istanbul University Istanbul Medical Faculty | Istanbul | 34093 | Turkey (Türkiye) |
| Dokuz Eylul Universitesi Tip Fakultesi | Izmir | 35340 | Turkey (Türkiye) |
| Erciyes University Medical Faculty | Talas | 38039 | Turkey (Türkiye) |
| University Hospitals Birmingham NHS Trust, | Birmingham | B15 2TH | United Kingdom |
| University College Hospital | London | NW1 2PG | United Kingdom |
| Derived |
| Suzuki K, Wechalekar AD, Kim K, Shimazaki C, Kim JS, Ikezoe T, Min CK, Zhou F, Cai Z, Chen X, Iida S, Katoh N, Fujisaki T, Shin HJ, Tran N, Qin X, Vasey SY, Tromp B, Weiss BM, Comenzo RL, Kastritis E, Lu J. Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA. Ann Hematol. 2023 Apr;102(4):863-876. doi: 10.1007/s00277-023-05090-z. Epub 2023 Mar 2. |
| 36444227 | Derived | Minnema MC, Dispenzieri A, Merlini G, Comenzo RL, Kastritis E, Wechalekar AD, Grogan M, Witteles R, Ruberg FL, Maurer MS, Tran N, Qin X, Vasey SY, Weiss BM, Vermeulen J, Jaccard A. Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis: Phase 3 ANDROMEDA Trial. JACC CardioOncol. 2022 Nov 15;4(4):474-487. doi: 10.1016/j.jaccao.2022.08.011. eCollection 2022 Nov. |
| 34192431 | Derived | Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schonland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021 Jul 1;385(1):46-58. doi: 10.1056/NEJMoa2028631. |
| 32244252 | Derived | Palladini G, Kastritis E, Maurer MS, Zonder J, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Bumma N, Kaufman JL, Medvedova E, Kovacsovics T, Rosenzweig M, Sanchorawala V, Qin X, Vasey SY, Weiss BM, Vermeulen J, Merlini G, Comenzo RL. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020 Jul 2;136(1):71-80. doi: 10.1182/blood.2019004460. |
| FG001 | 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). |
| FG002 | 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). |
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| COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | 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). |
| BG002 | 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). |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex/Gender, Customized | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Weight group in Kilograms (Kg) | Count of Participants | Participants |
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| Baseline Major Organ Involvement | Organ involvement assessment: biopsy. Heart: echo: mean wall thickness greater than (>) 12 millimeter, no other cardiac cause; kidney: 24- hour urine protein >0.5 gram per day, predominantly albumin; liver: total liver span >15 centimeter in absence of heart failure or alkaline phosphatase >1.5 times institutional upper limit of normal. | Count of Participants | Participants |
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| Number of Organs Involved | Mean | Standard Deviation | organs |
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| Number of Organs Involved | Number of participants whose 1 organ, 2 organs, 3 or more than 3 organs involved at baseline was reported. Organs like heart, kidney, and liver were considered. | Count of Participants | Participants |
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| Cardiac Stage Based on Mayo Clinic Cardiac Staging System | Cardiac stage is derived based on the combination of NT-proBNP (N-terminal pro b-type natriuretic peptide) and hs-cTnT (high sensitivity cardiac troponin T). Risk factor includes NT-proBNP >332 nanogram per liter (ng/L) and Hs-cTnT >54 ng/L. Stage I includes no markers above the cutoff, stage 2 includes one marker above the cutoff, stage 3a includes both markers above the cutoff, and stage 3b includes NT-proBNP >8500 ng/L and hs-cTnT >54 ng/L. | Count of Participants | Participants |
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| New York Heart Association (NYHA) Class | The NYHA classification: Class I- No symptoms and no limitation in ordinary physical activity, example, shortness of breath when walking, climbing stairs; class II- mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity; class IIIA- marked limitation in activity due to symptoms, even during less than ordinary activity, example, walking short distances (20-100 meter).Comfortable only at rest. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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). | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 2.4 years |
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| 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). | 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. | Posted | Median | 95% Confidence Interval | months | From date of first randomization (Day -3) upto 6.5 years |
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| Secondary | Overall Survival (OS) | Overall survival (OS) was measured from the date of randomization to the date of the participant's death. | 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. | Posted | Median | 95% Confidence Interval | Months | From date of first randomization (Day -3) up to 7.1 years |
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| 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). | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Month 6 |
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| 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Month 6 |
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| 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Month 6 |
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| 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). | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Month 6 |
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| 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. | 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. | Posted | Median | Full Range | Days | From date of first randomization (Day -3) up to 6.5 years |
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| 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. | 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. | Posted | Median | Full Range | Months | From date of first randomization (Day -3) up to 6.5 years |
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| 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. | 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. | Posted | Median | Full Range | Months | From date of first randomization (Day -3) up to 6.5 years |
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| 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. | 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. | Posted | Median | Full Range | Months | From date of first randomization (Day -3) up to 6.5 years |
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| 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. | 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. | Posted | Median | 95% Confidence Interval | Months | From date of first randomization (Day -3) up to 6.5 years |
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| 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. | 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. | Posted | Median | 95% Confidence Interval | Months | From date of first randomization (Day -3) up to 6.5 years |
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| 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | From date of first randomization (Day -3) up to 6.5 years |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Score on scale | 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 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Score on scale | 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 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Score on scale | 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 |
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All cause mortality: From baseline (Day -28) up to 7.1 years; Serious and Other AEs: For CyBorD: From start of treatment (Day 1) up to 30 days after last dose of study drug ( up to 8.33 months). Daratumumab plus CyBorD: From start of treatment (Day 1) up to 30 days after last dose of study drug ( up to 27.7 months).
All cause mortality: All participants randomized into the study. Serious and Other AEs: Safety analysis set was defined as participants who have received at least 1 administration of any study treatment (partial or complete).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). | 11 | 28 | 12 | 28 | 27 | 28 |
| EG001 | 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). | 67 | 193 | 68 | 188 | 181 | 188 |
| EG002 | 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). | 47 | 195 | 91 | 193 | 184 | 193 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Haemorrhagic Diathesis | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Acute Left Ventricular Failure | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Acute Myocardial Infarction | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Angina Pectoris | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Arrhythmia | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Arteriospasm Coronary | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Atrial Fibrillation | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Atrial Flutter | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Atrial Tachycardia | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Atrial Thrombosis | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Bradyarrhythmia | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Cardiac Arrest | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Cardiac Failure | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Cardiac Failure Congestive | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Cardiogenic Shock | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Cardiomyopathy | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Cardiovascular Insufficiency | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Coronary Artery Disease | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Left Ventricular Dysfunction | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Mitral Valve Incompetence | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
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| Myocardial Infarction | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Sinus Bradycardia | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Sinus Node Dysfunction | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Sinus Tachycardia | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Supraventricular Tachycardia | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hereditary Haemorrhagic Telangiectasia | Congenital, familial and genetic disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Amaurosis Fugax | Eye disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Colitis Ischaemic | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Gastric Haemorrhage | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Gastric Ulcer | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Intestinal Obstruction | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Chest Pain | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| General Physical Health Deterioration | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Multiple Organ Dysfunction Syndrome | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Non-Cardiac Chest Pain | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Peripheral Swelling | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Sudden Cardiac Death | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Sudden Death | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Bile Duct Stone | Hepatobiliary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hepatomegaly | Hepatobiliary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Adenovirus Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Biliary Sepsis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Candida Sepsis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Escherichia Bacteraemia | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Gastrointestinal Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Lower Respiratory Tract Infection Viral | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Neutropenic Sepsis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Orchitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pneumonia Pneumococcal | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pulmonary Sepsis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pyelonephritis Acute | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Respiratory Syncytial Virus Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Respiratory Tract Infection Viral | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Rhinovirus Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Wound Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Delayed Engraftment | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Femoral Neck Fracture | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Head Injury | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hip Fracture | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Rib Fracture | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Skin Laceration | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Traumatic Liver Injury | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Influenza A Virus Test Positive | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Diabetes Mellitus | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Failure to Thrive | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Fluid Overload | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyperglycaemic Hyperosmolar Nonketotic Syndrome | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Connective Tissue Inflammation | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Basal Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Bladder Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Cerebrovascular Accident | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Facial Paralysis | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Ischaemic Stroke | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Peripheral Sensorimotor Neuropathy | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Status Epilepticus | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Depressed Mood | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Mental Status Changes | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Suicide Attempt | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Chronic Kidney Disease | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Nephropathy | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Nephrotic Syndrome | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Renal Failure | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Renal Impairment | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Female Genital Tract Fistula | Reproductive system and breast disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Acute Pulmonary Oedema | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Acute Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Lung Disorder | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pneumonia Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pulmonary Haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pulmonary Oedema | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Skin Mass | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Elective Surgery | Surgical and medical procedures | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Circulatory Collapse | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Orthostatic Hypotension | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Eosinopenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dry Eye | Eye disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Ocular Hyperaemia | Eye disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Abdominal Distension | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Gastrointestinal Pain | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Injection Site Bruising | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Injection Site Discolouration | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Injection Site Erythema | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Non-Cardiac Chest Pain | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Tooth Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Skin Laceration | Injury, poisoning and procedural complications | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Basophil Count Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Blood Alkaline Phosphatase Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Blood Creatinine Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Gamma-Glutamyltransferase Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hepatic Enzyme Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Monocyte Count Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Weight Increased | Investigations | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Joint Swelling | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Memory Impairment | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Peripheral Sensory Neuropathy | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Confusional State | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Renal Impairment | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Urinary Incontinence | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Urinary Retention | Renal and urinary disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dyspnoea Exertional | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Rash Pruritic | Skin and subcutaneous tissue disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hot Flush | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
| |
| Orthostatic Hypotension | Vascular disorders | MedDRA Version 22.1 | Non-systematic Assessment |
|
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 in writing, such publication will be withheld for up to an additional 60 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director | Janssen Research & Development, LLC | 844-434-4210 | ClinicalTrialDisclosure@its.jnj.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 4, 2020 | Feb 11, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000686 | Amyloidosis |
| ID | Term |
|---|---|
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D000069286 | Bortezomib |
| D003907 | Dexamethasone |
| C556306 | daratumumab |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
Not provided
Not provided
| Male |
|
| Undifferentiated Sex |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| BELGIUM |
|
| BRAZIL |
|
| CANADA |
|
| CHINA |
|
| DENMARK |
|
| FRANCE |
|
| GERMANY |
|
| GREECE |
|
| HUNGARY |
|
| ISRAEL |
|
| ITALY |
|
| JAPAN |
|
| MEXICO |
|
| NETHERLANDS |
|
| POLAND |
|
| SOUTH KOREA |
|
| SPAIN |
|
| SWEDEN |
|
| TURKEY |
|
| UNITED KINGDOM |
|
| UNITED STATES |
|
| >65 to 85 kg |
|
| >85 kg |
|
| Baseline Organ Involvement: Kidney |
|
| Baseline Organ Involvement: Liver |
|
| 2 Organs |
|
| >=3 Organ |
|
| Class II |
|
| Class IIIa |
|
| Class IIIb |
|
| Class II |
|
| Class IIIA |
|
| OG001 | 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). |
|
|
|
|
| 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). |
|
|
|
|
|
|
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).
|
|
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).
|
|
|
|
|
|
|
|
|
|
|
|
| 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). |
|
|
| OG001 | 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). |
|
|
| OG001 | 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). |
|
|
| OG001 | 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). |
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