AL Amyloidosis Clinical Trial
A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis
Summary
The purpose of this study is to characterize cardiac safety of Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone (D-VCd) treatment regimens (Arm A: daratumumab + immediate VCd treatment and Arm B: daratumumab + deferred VCd) in newly diagnosed systemic amyloid light chain (AL) amyloidosis with cardiac involvement and to identify potential mitigation strategies for cardiac toxicity (cohort 1); to characterize the pharmacokinetics of subcutaneous (SC) daratumumab, among racial and ethnic minorities, including Black or African American, with newly diagnosed AL amyloidosis treated with D-VCd (cohort 2).
Eligibility Criteria
Inclusion Criteria:
Cohort 1: Cardiac involvement (amyloid light chain [AL] amyloidosis Mayo Cardiac Stage II and Stage IIIa) with or without other organ(s) involved; Cohort 2: One or more organs impacted by systemic AL amyloidosis according to consensus guidelines
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer
Cohort 2 only: self-identified racial and ethnic minorities, including Black or African American
Measurable disease at screening defined by one of the following:
Difference between iFLC and uninvolved FLC (dFLC) >= 40mg/L per central laboratory Serum involved free light chain (iFLC) >= 40 mg/L with an abnormal kappa:lambda ratio Serum M-protein >= 0.5 g/dL
Exclusion Criteria:
Prior therapy for systemic AL amyloidosis or multiple myeloma including medications that target cluster of differentiation 38 (CD38), with the exception of 160 milligrams(mg) dexamethasone or equivalent corticosteroid maximum exposure prior to randomization/enrollment
Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, >=60% plasma cells in the bone marrow, or hypercalcemia related to myeloma.
Participant received any of the following therapies:
treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less;
vaccinated with an investigational vaccine (except for COVID-19) live, attenuated or replicating viral vector vaccines less than (<) 4 weeks prior to randomization/enrollment. Participants who are taking strong Cytochrome P450 3A4(CYP3A4) inducers must discontinue their use at least 5 half-lives prior to the first dose of bortezomib
Stem cell transplantation -Planned stem cell transplant during the first 9 cycles of protocol therapy are excluded. Stem cell collection during the first 9 cycles of protocol therapy is permitted
Grade 2 sensory or Grade 1 painful peripheral neuropathy
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There are 45 Locations for this study
Duarte California, 91010, United States
New Haven Connecticut, 06510, United States
Tampa Florida, 33612, United States
Atlanta Georgia, 30322, United States
Boston Massachusetts, 02111, United States
Boston Massachusetts, 02118, United States
Detroit Michigan, 48201, United States
New York New York, 10021, United States
Charlotte North Carolina, 28204, United States
Cleveland Ohio, 44106, United States
Columbus Ohio, 43214, United States
Pittsburgh Pennsylvania, 15224, United States
Dallas Texas, 75390, United States
Richmond Virginia, 23219, United States
Seattle Washington, 90805, United States
Calgary Alberta, T2N 4, Canada
Edmonton Alberta, T6G 1, Canada
Toronto Ontario, M5G 2, Canada
Beijing , 10003, China
Beijing , 10004, China
Chengdu , 61004, China
Hangzhou , 31002, China
Shanghai , 20002, China
Limoges Cedex , 87042, France
Pierre Benite cedex , 69495, France
Poitiers , 86000, France
Toulouse , 31400, France
Berlin , 12203, Germany
Essen , 45122, Germany
Heidelberg , 69120, Germany
Athens , 11528, Greece
Napoli , 80131, Italy
Pavia , 27100, Italy
Roma , 00161, Italy
Groningen , 9713 , Netherlands
Maastricht , 6229 , Netherlands
Utrecht , 3584 , Netherlands
Badalona , 08916, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Madrid , 28027, Spain
Pamplona , 31008, Spain
Salamanca , 37007, Spain
Leicester , LE1 5, United Kingdom
London , NW1 2, United Kingdom
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