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

NCT ID: NCT05250973

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

151 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-01

Study Completion Date

2027-03-02

Brief Summary

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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).

Detailed Description

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Conditions

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Amyloidosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants of Cohort 1 will be randomized to either Arm A or Arm B of Cohort 1 in a 2:1 ratio. For Cohort 2, participants will be enrolled without randomization.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd)

Participants with newly diagnosed systemic amyloid light chain (AL) amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive daratumumab 1800 milligrams (mg) subcutaneously (SC) starting on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square \[mg/m\^2\] either orally or intravenously \[IV\], bortezomib 1.3 mg/m\^2 SC or IV, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22).

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

Daratumumab will be administered subcutaneously.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be administered either orally or IV.

Bortezomib

Intervention Type DRUG

Bortezomib will be administered by SC injection or IV.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered orally or IV.

Cohort1 (Arm B): Daratumumab + Deferred VCd

Participants with newly diagnosed systemic AL amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive SC daratumumab 1800mg on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (Cyclophosphamide 300 mg/m\^2 either orally or IV, Bortezomib 1.3 mg/m\^2 SC or IV, Dexamethasone 40 mg weekly either orally or IV) starting at Cycle 4 Day 1, weekly (Days 1, 8, 15, 22) in every 28-day cycle for a maximum of 6 cycles (Cycle 9 Day 22).

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

Daratumumab will be administered subcutaneously.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be administered either orally or IV.

Bortezomib

Intervention Type DRUG

Bortezomib will be administered by SC injection or IV.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered orally or IV.

Cohort 2: Daratumumab + VCd

Participants with racial and ethnic minorities, including Black or African American participants, with newly diagnosed AL amyloidosis will receive SC injection of daratumumab 1800 mg SC on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square \[mg/m\^2\] either orally or intravenously \[IV\], bortezomib 1.3 mg/m\^2 SC or IV, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22).

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

Daratumumab will be administered subcutaneously.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be administered either orally or IV.

Bortezomib

Intervention Type DRUG

Bortezomib will be administered by SC injection or IV.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered orally or IV.

Interventions

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Daratumumab

Daratumumab will be administered subcutaneously.

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide will be administered either orally or IV.

Intervention Type DRUG

Bortezomib

Bortezomib will be administered by SC injection or IV.

Intervention Type DRUG

Dexamethasone

Dexamethasone will be administered orally or IV.

Intervention Type DRUG

Other Intervention Names

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JNJ-54767414

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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City of Hope

Duarte, California, United States

Site Status

Smilow Cancer Hospital/Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Winship Cancer Institute Emory University

Atlanta, Georgia, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Boston University Medical Center

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Memorial Sloan Kettering

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Wake Forest University - Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

University Hospital of Cleveland

Cleveland, Ohio, United States

Site Status

Ohio Health Research Institute

Columbus, Ohio, United States

Site Status

West Penn Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

VCU Medical Center

Richmond, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Tom Baker Cancer Center

Calgary, Alberta, Canada

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

University Health Network UHN Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Peking University First Hospital

Beijing, , China

Site Status

Peking University People s Hospital

Beijing, , China

Site Status

West China Hospital Si Chuan University

Chengdu, , China

Site Status

First affiliated Hospital of Zhejiang University

Hangzhou, , China

Site Status

Ruijin Hospital Shanghai Jiao Tong University

Shanghai, , China

Site Status

CHU de Limoges

Limoges, , France

Site Status

Centre hospitalier Lyon-Sud

Pierre-Bénite, , France

Site Status

CHU De Poitiers

Poitiers, , France

Site Status

CHU Rangueil

Toulouse, , France

Site Status

Charite Campus Benjamin Franklin

Berlin, , Germany

Site Status

Universitatsklinikum Essen

Essen, , Germany

Site Status

Universitaetsklinikum Heidelberg Medizinische Klinik V

Heidelberg, , Germany

Site Status

Alexandra General Hospital of Athens

Athens, , Greece

Site Status

Università Degli Studi Di Napoli Federico Ii

Napoli, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

DIPARTIMENTO DI BIOTECNOLOGIE CELLULARI ED EMATOLOGIA - UNIVERSITà ''LA SAPIENZA''

Roma, , Italy

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Hospital Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

Hosp. Univ. Germans Trias I Pujol

Badalona, , Spain

Site Status

Hosp Univ Vall D Hebron

Barcelona, , Spain

Site Status

Hosp Clinic de Barcelona

Barcelona, , Spain

Site Status

Clinica Univ. de Navarra

Madrid, , Spain

Site Status

Clinica Univ. de Navarra

Pamplona, , Spain

Site Status

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Site Status

Leicester Royal Infirmary - Haematology

Leicester, , United Kingdom

Site Status

University College Hospital

London, , United Kingdom

Site Status

Countries

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United States Canada China France Germany Greece Italy Netherlands Spain United Kingdom

Other Identifiers

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54767414AMY2009

Identifier Type: OTHER

Identifier Source: secondary_id

2021-002639-48

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-507069-25-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR109160

Identifier Type: -

Identifier Source: org_study_id