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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03201965
Other study ID # CR108193
Secondary ID 2016-001737-2754
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date October 5, 2017
Est. completion date August 16, 2024

Study information

Verified date June 2024
Source Janssen Research & Development, LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of daratumumab plus cyclophosphamide, bortezomib and dexamethasone (CyBorD) compared with CyBorD alone in treatment of newly diagnosed amyloid light chain (AL) amyloidosis participants.


Description:

Participant involved in study for approx. 8 years duration includes Screening Phase (complete clinical evaluation will be done), Treatment Phase (monitoring of adverse events (AEs), laboratory abnormalities and clinical response), Post-Treatment Observation Phase (disease evaluations will be done) and a Long-term Follow-up Phase (Subsequent anticancer treatment, response to subsequent treatment, date of progression and survival status will be obtained every 16 weeks).The primary hypothesis is that daratumumab in combination with CyBorD will improve the overall complete hematological response rate compared to CyBorD alone in AL amyloidosis participants. Safety will be assessed by AEs, laboratory test results, electrocardiogram, vital sign measurements, physical examination, and Eastern Cooperative Oncology Group (ECOG) performance status.


Recruitment information / eligibility

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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Cyclophosphamide
Participants will receive 300 mg/m^2 of cyclophosphamide as an oral or IV dose.
Bortezomib
Participants will receive 1.3 mg/m^2 of bortezomib as an subcutaneous (SC) injection.
Dexamethasone, 40 mg
Participants of CyBorD alone arm will receive 40 mg dexamethasone orally or IV dose. Participants of CyBorD plus daratumumab arm will receive dexamethasone 20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing to make a total of 40 mg.
Daratumumab
Participants will receive 1800 mg of daratumumab subcutaneously.

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

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, 

Outcome

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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