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Clinical Trials in the UK / NCT05250973
Active, not recruiting Phase 2

A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis

NCT05250973 · tracked via the Priya Life Science UK tracker
Sponsor
Janssen Research & Development, LLC
Phase
Phase 2
Started
2022-03-01
Last updated
2026-08-28

Condition(s) studied

Amyloidosis

Investigational drug(s) / intervention(s)

DaratumumabCyclophosphamideBortezomibDexamethasone

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)

Trial sites (46)

FacilityCityRegionStatus
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.

On this site

📄 Darzalex (daratumumab) drug profile →

More Janssen Research & Development, LLC trials in the UK

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Official registry record

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.

View NCT05250973 on ClinicalTrials.gov ↗ ← All trials in the UK