Daratumumab: Daratumumab will be administered subcutaneously.
Cyclophosphamide: Cyclophosphamide will be administered either orally or IV.
Bortezomib: Bortezomib will be administered by SC injection or IV.
Dexamethasone: Dexamethasone will be administered orally or IV.
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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:
1. treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less;
2. 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
Primary outcome measure(s)
Number of Participants with Cardiac Events of Any Toxicity Grade — Up to 12 months Number of participants with cardiac events of any toxicity grade will be reported.
Observed Concentration Immediately Prior to the Next Study Treatment Administration (Ctrough) of Daratumumab — Cycle 3 Day 1 predose (each cycle is of 28 days) Ctrough is defined as the observed concentration immediately prior to the next study treatment administration.
Trial sites (46)
Facility
City
Region
Status
City of Hope
Duarte
California
Yale
New Haven
Connecticut
Moffitt Cancer Center
Tampa
Florida
Winship Cancer Institute Emory University
Atlanta
Georgia
Tufts Medical Center
Boston
Massachusetts
Boston University Medical Center
Boston
Massachusetts
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
Memorial Sloan Kettering
New York
New York
Levine Cancer Institute
Charlotte
North Carolina
Wake Forest University - Baptist Medical Center
Winston-Salem
North Carolina
University Hospital of Cleveland
Cleveland
Ohio
Ohio Health Research Institute
Columbus
Ohio
West Penn Hospital
Pittsburgh
Pennsylvania
UT Southwestern Medical Center
Dallas
Texas
VCU Medical Center
Richmond
Virginia
University of Washington
Seattle
Washington
Tom Baker Cancer Center
Calgary
Alberta
Cross Cancer Institute
Edmonton
Alberta
University Health Network UHN Princess Margaret Cancer Centre
Toronto
Ontario
Peking University First Hospital
Beijing
China
Peking University People's Hospital
Beijing
China
West China Hospital Si Chuan University
Chengdu
China
First affiliated Hospital of Zhejiang University
Hangzhou
China
Ruijin Hospital Shanghai Jiao Tong University
Shanghai
China
CHU de Limoges
Limoges
France
Centre hospitalier Lyon-Sud
Pierre-Bénite
France
CHU De Poitiers
Poitiers
France
CHU Rangueil
Toulouse
France
Charite Campus Benjamin Franklin
Berlin
Germany
Universitatsklinikum Essen
Essen
Germany
Universitaetsklinikum Heidelberg Medizinische Klinik V
Heidelberg
Germany
Alexandra General Hospital of Athens
Athens
Greece
Università Degli Studi Di Napoli Federico Ii
Naples
Italy
Fondazione IRCCS Policlinico San Matteo
Pavia
Italy
DIPARTIMENTO DI BIOTECNOLOGIE CELLULARI ED EMATOLOGIA - UNIVERSITà ''LA SAPIENZA''
Roma
Italy
University Medical Center Groningen
Groningen
Netherlands
Hospital Maastricht University Medical Center
Maastricht
Netherlands
UMC Utrecht
Utrecht
Netherlands
Hosp. Univ. Germans Trias I Pujol
Badalona
Spain
Hosp Univ Vall D Hebron
Barcelona
Spain
+ 6 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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