150 Participants Needed

Daratumumab Combination Therapy for Amyloidosis

(AQUARIUS Trial)

Recruiting at 49 trial locations
SC
Overseen ByStudy Contact
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Janssen Research & Development, LLC
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of four drugs on patients with a specific heart-related disease. The drugs work together to attack abnormal cells and reduce inflammation. The study aims to ensure the treatment is safe for the heart and understand how it behaves in different racial and ethnic groups.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking strong CYP3A4 inducers, you must stop them at least 5 half-lives before starting bortezomib.

Is daratumumab combination therapy safe for humans?

Daratumumab combination therapy, when used with bortezomib, cyclophosphamide, and dexamethasone, has been shown to have an acceptable safety profile in clinical trials for amyloidosis, with no new safety concerns compared to its use in other conditions like multiple myeloma. The treatment was generally well tolerated, with some patients experiencing mild infusion-related reactions.12345

What makes the daratumumab combination therapy unique for treating amyloidosis?

The daratumumab combination therapy is unique because it adds daratumumab, a CD38-targeting antibody, to the standard treatment of bortezomib, cyclophosphamide, and dexamethasone, significantly improving complete response rates and organ responses in patients with systemic AL amyloidosis, as shown in the ANDROMEDA trial.14678

What data supports the effectiveness of the drugs used in the Daratumumab Combination Therapy for Amyloidosis?

Research shows that bortezomib, one of the drugs in the combination, is effective when used with other cancer treatments, suggesting it may enhance the effectiveness of the combination therapy. Additionally, dexamethasone is used to prevent side effects in other treatments, indicating its supportive role in combination therapies.910111213

Who Is on the Research Team?

JR

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed AL amyloidosis affecting the heart and possibly other organs. Participants should be able to perform light activities (ECOG score 0-2). Women must test negative for pregnancy and agree to regular tests; men must not donate sperm during and after the study. Racial/ethnic minorities, including Black or African American individuals, are specifically included in one cohort.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.
One of my organs is affected by AL amyloidosis.
I am a woman who can have children, have tested negative for pregnancy, and agree to ongoing pregnancy tests.
See 3 more

Exclusion Criteria

I haven't used any experimental drugs or devices, or had certain vaccines recently.
I am not planning a stem cell transplant within the first 9 treatment cycles, but collection is okay.
I have had treatment for AL amyloidosis or multiple myeloma, but not more than 160mg dexamethasone.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab and VCd treatment regimens. In Arm A, VCd is administered immediately, while in Arm B, VCd is deferred. Cohort 2 focuses on racial and ethnic minorities.

Up to 24 cycles (28-day cycles)
Weekly visits for the first 2 cycles, bi-weekly for cycles 3-6, and monthly for cycles 7-24

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiac safety and pharmacokinetics.

Up to 12 months

Long-term Follow-up

Participants are monitored for long-term outcomes such as overall survival and organ response rate.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

  • Bortezomib
  • Cyclophosphamide
  • Daratumumab
  • Dexamethasone
Trial Overview The trial studies Daratumumab-based therapies in two groups: one receives immediate treatment with Daratumumab combined with Cyclophosphamide, Bortezomib, Dexamethasone (D-VCd), while the other has deferred VCd treatment. It aims to assess cardiac safety and understand how different populations process the drug.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Cohort1 (Arm B): Daratumumab + Deferred VCdExperimental Treatment4 Interventions
Group II: Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd)Experimental Treatment4 Interventions
Group III: Cohort 2: Daratumumab + VCdExperimental Treatment4 Interventions

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

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Approved in European Union as Velcade for:
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Approved in United States as Velcade for:
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Approved in Canada as Velcade for:
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Approved in Japan as Velcade for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials
1,022
Recruited
6,408,000+
Joaquin Duato profile image

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD profile image

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Combining bortezomib with trastuzumab significantly enhances the effectiveness of trastuzumab in HER-2-positive breast cancer cells, demonstrating a synergistic effect that leads to increased apoptosis at low drug concentrations.
The mechanism behind this enhanced efficacy involves the targeting of NF-kappaB activation and the localization of the cyclin-dependent kinase inhibitor p27, suggesting a promising avenue for improving treatment outcomes in patients with metastatic breast cancer.
Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner.Cardoso, F., Durbecq, V., Laes, JF., et al.[2020]
In a study of 493 patients with HER2-amplified early stage breast cancer, a regimen of docetaxel and cyclophosphamide combined with trastuzumab resulted in a high 2-year disease-free survival (DFS) rate of 97.8% for TOP2A-amplified patients and 97.9% for TOP2A-non-amplified patients, indicating its efficacy regardless of TOP2A status.
The treatment was generally well-tolerated, with common side effects including fatigue and neutropenia; however, 6% of patients experienced cardiac dysfunction, highlighting the need for monitoring during treatment.
Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study.Jones, SE., Collea, R., Paul, D., et al.[2022]
In a phase II study involving 69 patients with metastatic HER2-positive breast cancer, the combination of weekly paclitaxel, trastuzumab, and pertuzumab achieved an impressive 6-month progression-free survival (PFS) rate of 86%, indicating strong efficacy.
The treatment was well tolerated, with no cases of febrile neutropenia or symptomatic left ventricular dysfunction reported, suggesting it may be a safer alternative to traditional docetaxel-based therapies.
Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.Dang, C., Iyengar, N., Datko, F., et al.[2022]

Citations

Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner. [2020]
Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. [2022]
Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. [2022]
Single premedication dose of dexamethasone 20 mg IV before docetaxel administration. [2018]
Review of docetaxel (Taxotere), a highly active new agent for the treatment of metastatic breast cancer. [2018]
Daratumumab: A Review in Newly Diagnosed Systemic Light Chain Amyloidosis. [2022]
Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. [2021]
Health-related quality of life in patients with light chain amyloidosis treated with bortezomib, cyclophosphamide, and dexamethasone ± daratumumab: Results from the ANDROMEDA study. [2022]
High rate of profound clonal and renal responses with daratumumab treatment in heavily pre-treated patients with light chain (AL) amyloidosis and high bone marrow plasma cell infiltrate. [2020]
Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA. [2023]
11.United Statespubmed.ncbi.nlm.nih.gov
Daratumumab Plus Bortezomib and Dexamethasone in Newly Diagnosed Systemic Light Chain Amyloidosis. [2023]
Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. [2021]
Daratumumab plus CyBorD for patients with newly diagnosed light chain (AL) amyloidosis. [2021]
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