AL Amyloidosis Clinical Trial
A 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 Amyloid Light-chain (AL) Amyloidosis
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.
Full 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.
Eligibility Criteria
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:
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)
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:
NT-ProBNP > 8500 nanogram per liter (ng/L)
New York Heart Association (NYHA) classification IIIB or IV heart failure
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
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
For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization
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)
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
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:
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
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
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There are 140 Locations for this study
Phoenix Arizona, 85054, United States
Duarte California, 91010, United States
San Francisco California, 94143, United States
Stanford California, 94305, United States
Aurora Colorado, 80045, United States
Denver Colorado, 80218, United States
Jacksonville Florida, 32224, United States
Atlanta Georgia, 30322, United States
Baltimore Maryland, 21201, United States
Boston Massachusetts, 02111, United States
Boston Massachusetts, 02118, United States
Boston Massachusetts, 02215, United States
Detroit Michigan, 48201, United States
Rochester Minnesota, 55905, United States
Saint Louis Missouri, 63110, United States
New York New York, 10032, United States
New York New York, 10065, United States
Rochester New York, 14642, United States
Charlotte North Carolina, 28204, United States
Winston-Salem North Carolina, 27157, United States
Cleveland Ohio, 44195, United States
Columbus Ohio, 43210, United States
Portland Oregon, 97239, United States
Philadelphia Pennsylvania, 19104, United States
Nashville Tennessee, 37203, United States
Nashville Tennessee, 37232, United States
Houston Texas, 77030, United States
Salt Lake City Utah, 84112, United States
Seattle Washington, 98109, United States
Box Hill , 3128, Australia
Nedlands , 6009, Australia
Westmead , 2145, Australia
Woolloongabba , 4102, Australia
Anderlecht , 1070, Belgium
Gent , 9000, Belgium
Kortrijk , 8500, Belgium
Leuven , 3000, Belgium
Porto Alegre , 90035, Brazil
Recife , 50040, Brazil
Rio de Janeiro , 22775, Brazil
Salvador , 41253, Brazil
Sao Jose do Rio Preto , 15090, Brazil
Sao Paulo , 04039, Brazil
São Paulo , 01455, Brazil
São Paulo , 05403, Brazil
Calgary Alberta, T2N 4, Canada
Edmonton Alberta, T6G 1, Canada
Vancouver British Columbia, V5Z 1, Canada
London Ontario, N6A 5, Canada
Toronto Ontario, M5G 2, Canada
Montreal Quebec, H4A 3, Canada
Beijing , 10003, China
Beijing , 10004, China
Hangzhou , 31002, China
Shanghai , 20002, China
Wenzhou , 32500, China
Aarhus C , 8000, Denmark
Copenhagen , 2400, Denmark
Odense , 5000, Denmark
Dijon , 21000, France
Lille cedex , 59037, France
Limoges , 87000, France
Marseille , 13273, France
Nantes cedex 01 , 44035, France
PARIS cedex 10 , 75475, France
Pierre - Bénite cedex , 69495, France
Poitiers , 86000, France
Toulouse , 31400, France
Tours cedex , 37044, France
Vandoeuvre les Nancy , 54511, France
Berlin , 12203, Germany
Düsseldorf , 40225, Germany
Essen , 45122, Germany
Hamburg , 22767, Germany
Heidelberg , 69120, Germany
Tübingen , 72076, Germany
Würzburg , 97080, Germany
Athens , 11528, Greece
Patra , 26500, Greece
Budapest , 1083, Hungary
Budapest , 1088, Hungary
Budapest , 1097, Hungary
Haifa , 34362, Israel
Jerusalem , 91120, Israel
Ramat-Gan , 52621, Israel
Tel-Aviv , 64239, Israel
Zerifin , 70300, Israel
Bari , 70124, Italy
Bologna , 40138, Italy
Palermo , 90146, Italy
Pavia , 27100, Italy
Roma , 00161, Italy
Torino , 10126, Italy
Fukushima , 960-1, Japan
Hiroshima , 730-8, Japan
Hokkaido , 006-8, Japan
Kanazawa , 920-8, Japan
Kumamoto-City , 860-8, Japan
Kyoto , 603-8, Japan
Matsumoto , 390-8, Japan
Matsuyama , 790-8, Japan
Nagoya , 467 8, Japan
Okayama , 701-1, Japan
Shibuya , 150-8, Japan
Tokushima , 770-8, Japan
Busan , 49241, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 06351, Korea, Republic of
Seoul , 06591, Korea, Republic of
Guadalajara , 44160, Mexico
Monterrey , 64460, Mexico
Den Haag , 2545 , Netherlands
Groningen , 9713 , Netherlands
Rotterdam , 3015 , Netherlands
Utrecht , 3584 , Netherlands
Veldhoven , 5504 , Netherlands
Chorzów , 41-50, Poland
Poznan , 60-56, Poland
Warszawa , 02-77, Poland
Badalona , 08916, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Madrid , 28034, Spain
Madrid , 28040, Spain
Madrid , 28041, Spain
Pamplona , 31008, Spain
Salamanca , 37007, Spain
San Cristóbal de La Laguna , 38320, Spain
Valencia , 46017, Spain
Boras , 501 8, Sweden
Lund , 221 8, Sweden
Ankara , 06590, Turkey
Antalya , 7059, Turkey
Atakum , 55270, Turkey
Istanbul , 34093, Turkey
Izmir , 35340, Turkey
Talas , 38039, Turkey
Birmingham , B15 2, United Kingdom
London , NW1 2, United Kingdom
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