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AmyloidosisPhase 2AQUARIUSNCT05250973

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

A Phase 2 study testing Daratumumab, Cyclophosphamide and Bortezomib in people with Amyloidosis, run by Janssen Research & Development, LLC at 46 sites in 10 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Amyloidosis
What is being tested?
Daratumumab, Cyclophosphamide and Bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
151 participants
Where
46 sitesin 10 countries
Study dates
1 Mar 2022to 12 Nov 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

46 sites in 10 countries.

46 sites in 10 countries

United States16 sites

  • Winship Cancer Institute Emory University

    Atlanta, Georgia, 30322

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Boston University Medical Center

    Boston, Massachusetts, 02118

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • University Hospital of Cleveland

    Cleveland, Ohio, 44106

  • Ohio Health Research Institute

    Columbus, Ohio, 43214

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • Yale

    New Haven, Connecticut, 06520

  • Memorial Sloan Kettering

    New York, New York, 10065

  • West Penn Hospital

    Pittsburgh, Pennsylvania, 15224

  • VCU Medical Center

    Richmond, Virginia, 23298

  • University of Washington

    Seattle, Washington, 02118-3000

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Wake Forest University - Baptist Medical Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

Spain6 sites

  • Hosp. Univ. Germans Trias I Pujol

    Badalona, 08916

  • Hosp Univ Vall D Hebron

    Barcelona, 08035

  • Hosp Clinic de Barcelona

    Barcelona, 08036

  • Clinica Univ. de Navarra 1

    Madrid, 28027

  • Clinica Univ. de Navarra

    Pamplona, 31008

  • Hosp Clinico Univ de Salamanca

    Salamanca, 37007

Other trials in Spain

China5 sites

  • Peking University First Hospital

    Beijing, 100034

  • Peking University People's Hospital

    Beijing, 100044

  • West China Hospital Si Chuan University

    Chengdu, 610041

  • First affiliated Hospital of Zhejiang University

    Hangzhou, 310003

  • Ruijin Hospital Shanghai Jiao Tong University

    Shanghai, 200025

Other trials in China

France4 sites

  • CHU de Limoges

    Limoges, 87042

  • Centre hospitalier Lyon-Sud

    Pierre-Bénite, 69495

  • CHU De Poitiers

    Poitiers, 86000

  • CHU Rangueil

    Toulouse, 31400

Other trials in France

Canada3 sites

  • Tom Baker Cancer Center

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • University Health Network UHN Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Germany3 sites

  • Charite Campus Benjamin Franklin

    Berlin, 12203

  • Universitatsklinikum Essen

    Essen, 45122

  • Universitaetsklinikum Heidelberg Medizinische Klinik V

    Heidelberg, 69120

Other trials in Germany

Italy3 sites

  • Università Degli Studi Di Napoli Federico Ii

    Naples, 80131

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

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

    Roma, 00161

Other trials in Italy

Netherlands3 sites

  • University Medical Center Groningen

    Groningen, 9713 GZ

  • Hospital Maastricht University Medical Center

    Maastricht, 6229 HX

  • UMC Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

United Kingdom2 sites

  • Leicester Royal Infirmary - Haematology

    Leicester, LE1 5WW

  • University College Hospital

    London, NW1 2PG

Other trials in United Kingdom

Greece1 site

  • Alexandra General Hospital of Athens

    Athens, 11528

Other trials in Greece

About this study

Official title: A Phase 2, Multicohort Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis

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).

Conditions
Amyloidosis
Medical subject headings
Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaratumumabDrug

    Also called JNJ-54767414

    Daratumumab will be administered subcutaneously.

  • CyclophosphamideDrug

    Cyclophosphamide will be administered either orally or IV.

  • BortezomibDrug

    Bortezomib will be administered by SC injection or IV.

  • DexamethasoneDrug

    Dexamethasone will be administered orally or IV.

Study groups in NCT05250973
Study groupRoleWhat they receive
Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd)ExperimentalParticipants 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).
Receives: Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone
Cohort1 (Arm B): Daratumumab + Deferred VCdExperimentalParticipants 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).
Receives: Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone
Cohort 2: Daratumumab + VCdExperimentalParticipants 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).
Receives: Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with Cardiac Events of Any Toxicity Grade

    Number of participants with cardiac events of any toxicity grade will be reported.

    Measured: Up to 12 months

  2. Observed Concentration Immediately Prior to the Next Study Treatment Administration (Ctrough) of Daratumumab

    Ctrough is defined as the observed concentration immediately prior to the next study treatment administration.

    Measured: Cycle 3 Day 1 predose (each cycle is of 28 days)

Secondary outcomes (13)

  1. Overall Complete Hematologic Response (HemCR) Rate

    Overall HemCR rate is defined as percentage of participants who achieve HemCR during or after the study treatment.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  2. HemCR Rate

    HemCR rate at 6 month is defined as percentage of participants who achieve HemCR at 6 month during or after the study treatment.

    Measured: At 6 months

  3. Very Good Partial Response (VGPR) or Better Rate

    Hematologic greater than or equal to (>=) VGPR rate is defined as percentage of participants who achieve hematologic response of VGPR or better.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  4. Time to HemCR or (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).

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  5. Duration of Response (HemCR and VGPR or Better)

    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.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  6. Organ Response Rate (OrRR)

    Organ response rate is defined as the percentage of participants who achieve organ response in each corresponding organ (kidney, heart, liver).

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  7. Overall Survival (OS)

    OS is measured from the date of first study treatment to the date of the participant's death.

    Measured: Until Cycle 12 or Month 12 (whichever occurs later)

  8. Time to Subsequent Therapy

    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.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  9. Number of Participants with Adverse Events (AEs) by Severity

    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.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  10. Serum Concentration of Daratumumab

    Serum samples will be analyzed to determine concentrations of daratumumab.

    Measured: Up to 3 years

  11. Number of Participants with Antibodies to Daratumumab

    Number of participants with antibodies to daratumumab will be reported.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  12. Number of Participants with Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20)

    Number of participants with antibodies to rHuPH20 will be reported.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

  13. Change from Baseline in Clinical Signs and Symptoms Score of Cardiac AL Amyloidosis

    Change from baseline in clinical signs and symptoms score of cardiac AL amyloidosis will be reported.

    Measured: Up to Cycle 12 or Month 12 (whichever occurs later)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2022
  2. Study start1 Mar 2022
  3. Primary completion4 Feb 2026
  4. Study completion12 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05250973
Sponsor's protocol ID
CR109160
Other IDs
54767414AMY2009, 2021-002639-48, 2023-507069-25-00, 2023
Acronym
AQUARIUS
Status last verified
Nov 2026
First submitted
11 Feb 2022
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Cyclophosphamide and Bortezomib in people with Amyloidosis, run by Janssen Research & Development, LLC at 46 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in United States, Spain, China, France, Canada and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Cardiac Events of Any Toxicity Grade (time frame: Up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05250973.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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