Clinical Trial
Study Details
Dexamethasone will be administered orally or IV.
Outcomes
Number of participants with cardiac events of any toxicity grade will be reported.
Ctrough is defined as the observed concentration immediately prior to the next study treatment administration.
Overall HemCR rate is defined as percentage of participants who achieve HemCR during or after the study treatment.
HemCR rate at 6 month is defined as percentage of participants who achieve HemCR at 6 month during or after the study treatment.
Hematologic greater than or equal to (\>=) VGPR rate is defined as percentage of participants who achieve hematologic response of VGPR or better.
For participants who achieve HemCR (or \>=VGPR), time to HemCR (or \>=VGPR) is defined as the time between the date of first study treatment and the first efficacy evaluation at which the participant has met all criteria for hematologic complete response (CR) (or \>=VGPR).
For participants who achieve HemCR (or \>=VGPR), duration of HemCR (or \>=VGPR) is defined as the time between the date of initial documentation of HemCR (or \>=VGPR) to the date of first documented evidence of hematologic progressive disease or death, whichever comes first.
Organ response rate is defined as the percentage of participants who achieve organ response in each corresponding organ (kidney, heart, liver).
OS is measured from the date of first study treatment to the date of the participant's death.
Time to subsequent therapy for amyloid light chain (AL) amyloidosis is defined as the time from the date of first study treatment to the start date of subsequent AL amyloidosis (non-protocol) treatment.
Number of participants with AEs by severity will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
Serum samples will be analyzed to determine concentrations of daratumumab.
Number of participants with antibodies to daratumumab will be reported.
Number of participants with antibodies to rHuPH20 will be reported.
Change from baseline in clinical signs and symptoms score of cardiac AL amyloidosis will be reported.
Study Overview
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).
Contacts and Locations
City of Hope
Duarte, CA 91010
United States
Smilow Cancer Hospital/Yale Cancer Center
New Haven, CT 06510
United States
Moffitt Cancer Center
Tampa, FL 33612
United States
Winship Cancer Institute Emory University
Atlanta, GA 30322
United States
Tufts Medical Center
Boston, MA 02111
United States
Boston University Medical Center
Boston, MA 02118
United States
Barbara Ann Karmanos Cancer Institute
Detroit, MI 48201
United States
Memorial Sloan Kettering
New York, NY 10021
United States
Levine Cancer Institute
Charlotte, NC 28204
United States
University Hospital of Cleveland
Cleveland, OH 44106
United States
Ohio Health Research Institute
Columbus, OH 43214
United States
West Penn Hospital
Pittsburgh, PA 15224
United States
UT Southwestern Medical Center
Dallas, TX 75390
United States
VCU Medical Center
Richmond, VA 23219
United States
University of Washington
Seattle, WA 90805
United States
Tom Baker Cancer Center
Calgary AB T2N 4N2
Canada
Cross Cancer Institute
Edmonton AB T6G 1Z2
Canada
University Health Network (UHN) Princess Margaret Cancer Centre
Toronto ON M5G 2M9
Canada
Peking University First Hospital
Beijing
100034
China
Peking University People s Hospital
Beijing
100044
China
West China Hospital Si Chuan University
Chengdu
610041
China
First affiliated Hospital of Zhejiang University
Hangzhou
310020
China
Ruijin Hospital, Shanghai Jiao Tong University
Shanghai
200025
China
CHU de Limoges
87042 Limoges Cedex
France
Centre hospitalier Lyon-Sud
69495 Pierre Benite cedex
France
CHU De Poitiers
86000 Poitiers
France
CHU Rangueil
31400 Toulouse
France
Charite Campus Benjamin Franklin
12203 Berlin
Germany
Universitatsklinikum Essen
45122 Essen
Germany
Universitaetsklinikum Heidelberg Medizinische Klinik V
69120 Heidelberg
Germany
Alexandra General Hospital of Athens
11528 Athens
Greece
Università Degli Studi Di Napoli Federico Ii
80131 Napoli
Italy
Fondazione IRCCS Policlinico San Matteo
27100 Pavia
Italy
DIPARTIMENTO DI BIOTECNOLOGIE CELLULARI ED EMATOLOGIA - UNIVERSITà ''LA SAPIENZA''
00161 Roma
Italy
University Medical Center Groningen
9713 GZ Groningen
Netherlands
Hospital Maastricht University Medical Center
6229 HX Maastricht
Netherlands
UMC Utrecht
3584 CX Utrecht
Netherlands
Hosp. Univ. Germans Trias I Pujol
08916 Badalona
Spain
Hosp. Univ. Vall D Hebron
08035 Barcelona
Spain
Hosp. Clinic de Barcelona
08036 Barcelona
Spain
Clinica Univ. de Navarra
28027 Madrid
Spain
Clinica Univ. de Navarra
31008 Pamplona
Spain
Hosp. Clinico Univ. de Salamanca
37007 Salamanca
Spain
Leicester Royal Infirmary - Haematology
Leicester
LE1 5WW
United Kingdom
University College Hospital
London
NW1 2PG
United Kingdom
Participation 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:
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