Amyloidosis Clinical Trial
Official title:
A Randomized Phase 3 Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic AL Amyloidosis
Verified date | June 2024 |
Source | Janssen Research & Development, LLC |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 416 |
Est. completion date | August 16, 2024 |
Est. primary completion date | February 14, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance - Measurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following: 1. serum monoclonal (M)-protein greater than or equal (>=) 0.5 grams/deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation [IFE] performed at a central laboratory) 2. serum free light chain greater than or equal to (>=) 50 milligram/Liter (mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) >= 50 mg/L - One or more organs impacted by AL amyloidosis according to consensus guidelines - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2 Exclusion Criteria: - Prior therapy for AL amyloidosis or multiple myeloma including medications that target CD38, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to randomization - Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, >= 60 percent (%) plasma cells in the bone marrow, or hypercalcemia - Evidence of significant cardiovascular conditions as specified below: 1. NT-ProBNP > 8500 nanogram per liter (ng/L) 2. New York Heart Association (NYHA) classification IIIB or IV heart failure 3. Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram [ECG] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy 4. Inpatient admission to a hospital for unstable angina or myocardial infarction within the last 6 months prior to first dose or percutaneous cardiac intervention with recent stent within 6 months or coronary artery bypass grafting within 6 months 5. For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization 6. Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillators [ICD] is indicated but not placed (participants who do have a pacemaker/ICD are allowed on study) 7. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 500 milliseconds (msec). Participants who have a pacemaker may be included regardless of calculated QTc interval 8. Supine systolic blood pressure < 90 millimeter of mercury (mmHg), or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 20 mmHg despite medical management (eg, midodrine, fludrocortisones) in the absence of volume depletion - Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted - Known to be seropositive for human immunodeficiency virus (HIV) - Any one of the following: 1. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded 2. Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy) - Grade 2 sensory or Grade 1 painful peripheral neuropathy |
Country | Name | City | State |
---|---|---|---|
Australia | Box Hill Hospital | Box Hill | |
Australia | Sir Charles Gairdner Hospital | Nedlands | |
Australia | Westmead Hospital | Westmead | |
Australia | Princess Alexandra Hospital | Woolloongabba | |
Belgium | Institut Jules Bordet | Anderlecht | |
Belgium | UZ Gent | Gent | |
Belgium | Az Groeninge | Kortrijk | |
Belgium | Universitair Ziekenhuis Leuven | Leuven | |
Brazil | Hospital das Clinicas de Porto Alegre | Porto Alegre | |
Brazil | Sociedade Pernambucana de Combate ao Cancer | Recife | |
Brazil | Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI) | Rio de Janeiro | |
Brazil | Hospital Sao Rafael | Salvador | |
Brazil | Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base | Sao Jose do Rio Preto | |
Brazil | Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE | Sao Paulo | |
Brazil | Clinica Sao Germano | São Paulo | |
Brazil | Hospital Das Clinicas Da Faculdade De Medicina Da USP | São Paulo | |
Canada | Alberta Health Services | Calgary | Alberta |
Canada | Alberta Health Services | Edmonton | Alberta |
Canada | London Health Sciences Center | London | Ontario |
Canada | McGill University Health Centre | Montreal | Quebec |
Canada | University Health Network UHN Princess Margaret Cancer Centre | Toronto | Ontario |
Canada | Vancouver General Hospital | Vancouver | British Columbia |
China | Peking University First Hospital | Beijing | |
China | Peking University People s Hospital | Beijing | |
China | First affiliated Hospital of Zhejiang University | Hangzhou | |
China | Ruijin Hospital Shanghai Jiao Tong University | Shanghai | |
China | The First Affiliated Hospital of Wenzhou Medical University | Wenzhou | |
Denmark | Aarhus University Hospital | Aarhus C | |
Denmark | Dep. of Hematology, Rigshospitalet | Copenhagen | |
Denmark | Odense Universitets Hospital | Odense | |
France | CHU Dijon | Dijon | |
France | Hopital Claude Huriez | Lille cedex | |
France | CHU de Limoges - Fédération Hépatologie | Limoges | |
France | Institut Paoli Calmettes | Marseille | |
France | Chu Hotel Dieu | Nantes cedex 01 | |
France | Hopital Saint Louis | PARIS cedex 10 | |
France | Centre hospitalier Lyon-Sud | Pierre - Bénite cedex | |
France | CHU De Poitiers | Poitiers | |
France | CHU Rangueil | Toulouse | |
France | CHU Bretonneau | Tours cedex | |
France | CHU de Nancy_ Hopital Brabois | Vandoeuvre les Nancy | |
Germany | Charite Campus Benjamin Franklin | Berlin | |
Germany | Heinrich-Heine-Universität Düsseldorf | Düsseldorf | |
Germany | Universitatsklinikum Essen | Essen | |
Germany | HOPA-Hämatologisch-Onkologische Praxis Altona MVZ GmbH | Hamburg | |
Germany | Universitaetsklinikum Heidelberg Medizinische Klinik V | Heidelberg | |
Germany | Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II, | Tübingen | |
Germany | Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii | Würzburg | |
Greece | Alexandra General Hospital of Athens | Athens | |
Greece | University General Hospital of Rio | Patra | |
Hungary | Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely | Budapest | |
Hungary | Semmelweis Egyetem I.Belgyogyaszati Klinika | Budapest | |
Hungary | Semmelweis Egyetem I.Belgyogyaszati Klinika | Budapest | |
Israel | Carmel Hospital | Haifa | |
Israel | Hadassah Medical Center | Jerusalem | |
Israel | Sheba Medical Center | Ramat-Gan | |
Israel | Sourasky Medical Center | Tel-Aviv | |
Israel | Assaf Ha'Rofeh Medical Center | Zerifin | |
Italy | Policlinico di Bari | Bari | |
Italy | Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi | Bologna | |
Italy | Casa di Cura La Maddalena | Palermo | |
Italy | Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo | Pavia | |
Italy | Dipartimento Di Biotecnologie Cellulari Ed Ematologia-Università ''La Sapienza'',Policlinico Umberto I | Roma | |
Italy | A.O.U. Città della Salute e della Scienza | Torino | |
Japan | Fukushima Medical University Hospital | Fukushima | |
Japan | Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital | Hiroshima | |
Japan | Teine Keijinkai Hospital | Hokkaido | |
Japan | Kanazawa University Hospital | Kanazawa | |
Japan | Kumamoto University Hospital | Kumamoto-City | |
Japan | Kyoto Kuramaguchi Medical Center | Kyoto | |
Japan | Shinshu University Hospital | Matsumoto | |
Japan | Matsuyama Red Cross Hospital | Matsuyama | |
Japan | Nagoya City University Hospital | Nagoya | |
Japan | National Hospital Organization Okayama Medical Center | Okayama | |
Japan | Japanese Red Cross Medical Center | Shibuya | |
Japan | Tokushima University Hospital | Tokushima | |
Korea, Republic of | Pusan National University Hospital | Busan | |
Korea, Republic of | Samsung Medical Center | Seoul | |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Korea, Republic of | Severance Hospital Yonsei University Health System | Seoul | |
Korea, Republic of | The Catholic University of Korea Seoul St. Mary's Hospital | Seoul | |
Mexico | Centro de Investigación Farmacéutica Especializada | Guadalajara | |
Mexico | Hospital Universitario Dr Jose Eleuterio Gonzalez | Monterrey | |
Netherlands | Haga ziekenhuis | Den Haag | |
Netherlands | UMCG | Groningen | |
Netherlands | Erasmus MC | Rotterdam | |
Netherlands | UMC Utrecht | Utrecht | |
Netherlands | Maxima Medisch Centrum | Veldhoven | |
Poland | Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich | Chorzów | |
Poland | SKPP UM w Poznaniu | Poznan | |
Poland | Instytut Hematologii i Transfuzjologii | Warszawa | |
Spain | Inst. Cat. D'Oncologia-Badalona | Badalona | |
Spain | Hosp Clinic de Barcelona | Barcelona | |
Spain | Hosp. Univ. Vall D Hebron | Barcelona | |
Spain | Hosp Univ Fund Jimenez Diaz | Madrid | |
Spain | Hosp. Univ. 12 de Octubre | Madrid | |
Spain | Hosp. Univ. Ramon Y Cajal | Madrid | |
Spain | Clinica Univ. de Navarra | Pamplona | |
Spain | Hosp Clinico Univ de Salamanca | Salamanca | |
Spain | Hosp. Univ. de Canarias | San Cristóbal de La Laguna | |
Spain | Hosp. Univ. Dr. Peset | Valencia | |
Sweden | South Elvsborg Hospital | Boras | |
Sweden | Skanes universitetssjukhus | Lund | |
Turkey | Ankara Universitesi Tip Fakultesi Cebeci Hastanesi | Ankara | |
Turkey | Akdeniz University Medical Faculty | Antalya | |
Turkey | Ondokuz Mayis Universitesi Tip Fakultesi | Atakum | |
Turkey | Istanbul University Istanbul Medical Faculty | Istanbul | |
Turkey | Dokuz Eylul Universitesi Tip Fakultesi | Izmir | |
Turkey | Erciyes University Medical Faculty | Talas | |
United Kingdom | University Hospitals Birmingham NHS Trust, | Birmingham | |
United Kingdom | University College Hospital | London | |
United States | Winship Cancer Institute Emory University | Atlanta | Georgia |
United States | University of Colorado | Aurora | Colorado |
United States | University of Maryland | Baltimore | Maryland |
United States | Boston University Medical Center | Boston | Massachusetts |
United States | Dana Farber Cancer Institute | Boston | Massachusetts |
United States | Tufts Medical Center | Boston | Massachusetts |
United States | Levine Cancer Institute | Charlotte | North Carolina |
United States | Cleveland Clinic | Cleveland | Ohio |
United States | The Ohio State University | Columbus | Ohio |
United States | Colorado Blood Cancer Institute | Denver | Colorado |
United States | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan |
United States | City of Hope | Duarte | California |
United States | University of Texas, MD Anderson Cancer Center | Houston | Texas |
United States | Mayo Clinic | Jacksonville | Florida |
United States | Sarah Cannon Research Institute | Nashville | Tennessee |
United States | Vanderbilt University Medical Center | Nashville | Tennessee |
United States | Columbia University Medical Center | New York | New York |
United States | Weill Cornell Medical College | New York | New York |
United States | University of Pennsylvania Medical Center | Philadelphia | Pennsylvania |
United States | Mayo Clinic Arizona | Phoenix | Arizona |
United States | Oregon Health And Science University | Portland | Oregon |
United States | Mayo Clinic Rochester | Rochester | Minnesota |
United States | University of Rochester Medical Center | Rochester | New York |
United States | Washington University School Of Medicine | Saint Louis | Missouri |
United States | Huntsman Cancer Institute | Salt Lake City | Utah |
United States | University of California San Francisco | San Francisco | California |
United States | Seattle Cancer Care Alliance | Seattle | Washington |
United States | Stanford University | Stanford | California |
United States | Wake Forest University Health Sciences - Cardiovascular Medicine | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Janssen Research & Development, LLC |
United States, Australia, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
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). | Up to 2.4 years |
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