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Proteasome Inhibitor

Daratumumab Combination Therapy for Amyloidosis (AQUARIUS Trial)

Phase 2
Recruiting
Research Sponsored by Janssen Research & Development, LLC
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
Cohort 1: Cardiac involvement (amyloid light chain [AL] amyloidosis Mayo Cardiac Stage II and Stage IIIa) with or without other organ(s) involved
Must not have
Grade 2 sensory or Grade 1 painful peripheral neuropathy
Previous or current diagnosis of symptomatic multiple myeloma per International Myeloma Working Group (IMWG) Criteria
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 3 years
Awards & highlights
No Placebo-Only Group

Summary

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.

Who is the study for?
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.
What is being tested?
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.
What are the potential side effects?
Potential side effects include reactions at injection sites, heart complications, blood disorders like low counts of various cells leading to increased infection risk or bleeding tendencies, nerve damage that could cause numbness or pain, muscle weakness, and possible harm to unborn babies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I can take care of myself and am up and about more than half of my waking hours.
Select...
My heart is affected by AL amyloidosis, at Stage II or IIIa.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
I experience mild numbness or mild pain in my hands or feet.
Select...
I have been diagnosed with symptomatic multiple myeloma.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 3 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Number of Participants with Cardiac Events of Any Toxicity Grade
Observed Concentration Immediately Prior to the Next Study Treatment Administration (Ctrough) of Daratumumab
Secondary study objectives
Change from Baseline in Clinical Signs and Symptoms Score of Cardiac AL Amyloidosis
Duration of Response (HemCR and VGPR or Better)
HemCR Rate
+10 more

Side effects data

From 2024 Phase 3 trial • 498 Patients • NCT02136134
44%
Thrombocytopenia
38%
Peripheral sensory neuropathy
38%
Peripheral Sensory Neuropathy
32%
Anaemia
24%
Fatigue
22%
Diarrhoea
17%
Upper respiratory tract infection
17%
Upper Respiratory Tract Infection
16%
Constipation
15%
Insomnia
15%
Asthenia
13%
Cough
11%
Nausea
11%
Neuralgia
11%
Pyrexia
11%
Dizziness
10%
Back pain
10%
Back Pain
10%
Pneumonia
10%
Neutropenia
9%
Dyspnoea
8%
Oedema peripheral
8%
Oedema Peripheral
7%
Pain in extremity
7%
Hyperglycaemia
6%
Pain in Extremity
6%
Arthralgia
6%
Headache
6%
Paraesthesia
6%
Bronchitis
5%
Bone pain
5%
Epistaxis
5%
Bone Pain
5%
Decreased Appetite
5%
Dyspepsia
5%
Hypocalcaemia
5%
Leukopenia
5%
Hypokalaemia
5%
Decreased appetite
4%
Lymphopenia
4%
Oedema
4%
Vomiting
4%
Hypotension
4%
Alanine aminotransferase increased
4%
Abdominal pain
4%
Nasopharyngitis
4%
Alanine Aminotransferase Increased
3%
Hypertension
3%
Hypophosphataemia
3%
Rash
3%
Abdominal Pain Upper
3%
Conjunctivitis
3%
Abdominal pain upper
3%
Influenza
2%
Muscle Spasms
2%
Musculoskeletal Chest Pain
2%
Muscle spasms
2%
Aspartate aminotransferase increased
2%
Urinary tract infection
2%
Myalgia
2%
Herpes zoster
2%
Musculoskeletal chest pain
2%
Herpes Zoster
1%
Pulmonary Embolism
1%
Weight Decreased
1%
Pulmonary embolism
1%
Myocardial infarction
1%
Dehydration
1%
Myocardial Infarction
1%
Lower Respiratory Tract Infection
1%
Abdominal Pain
1%
Orthostatic Hypotension
1%
General Physical Health Deterioration
1%
General physical health deterioration
1%
Hyponatraemia
1%
Condition aggravated
1%
Orthostatic hypotension
1%
Lower respiratory tract infection
1%
Syncope
1%
Productive cough
1%
Nasal congestion
1%
Respiratory failure
1%
Weight decreased
1%
Chills
1%
Gastroenteritis
1%
Sepsis
1%
Respiratory Failure
1%
Condition Aggravated
100%
80%
60%
40%
20%
0%
Study treatment Arm
Bortezomib + Dexamethasone (Vd)
Daratumumab + Bortezomib and Dexamethasone (DVd)
Switch From Bortezomib + Dexamethasone (Vd) to Daratumumab Monotherapy

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups
Experimental Treatment
Group I: Cohort1 (Arm B): Daratumumab + Deferred VCdExperimental Treatment4 Interventions
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 II: Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd)Experimental Treatment4 Interventions
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 III: Cohort 2: Daratumumab + VCdExperimental Treatment4 Interventions
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).
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Dexamethasone
2007
Completed Phase 4
~2650
Bortezomib
2005
Completed Phase 3
~1410
Daratumumab
2014
Completed Phase 3
~2000
Cyclophosphamide
2010
Completed Phase 4
~2310

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Daratumumab is an anti-CD38 monoclonal antibody that targets CD38 on plasma cells, leading to cell death through multiple mechanisms including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and apoptosis. Cyclophosphamide is an alkylating agent that interferes with DNA replication, causing cell death. Bortezomib is a proteasome inhibitor that disrupts protein degradation, leading to apoptosis of plasma cells. Dexamethasone is a corticosteroid that reduces inflammation and has cytotoxic effects on plasma cells. These mechanisms are crucial for Amyloidosis patients as they target the abnormal plasma cells responsible for producing the amyloid light chains, thereby reducing amyloid deposits and improving organ function.

Find a Location

Who is running the clinical trial?

Janssen Research & Development, LLCLead Sponsor
1,003 Previous Clinical Trials
6,397,846 Total Patients Enrolled
2 Trials studying Amyloidosis
596 Patients Enrolled for Amyloidosis
Janssen Research & Development, LLC Clinical TrialStudy DirectorJanssen Research & Development, LLC
769 Previous Clinical Trials
3,973,586 Total Patients Enrolled
2 Trials studying Amyloidosis
596 Patients Enrolled for Amyloidosis

Media Library

Bortezomib (Proteasome Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05250973 — Phase 2
Amyloidosis Research Study Groups: Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd), Cohort1 (Arm B): Daratumumab + Deferred VCd, Cohort 2: Daratumumab + VCd
Amyloidosis Clinical Trial 2023: Bortezomib Highlights & Side Effects. Trial Name: NCT05250973 — Phase 2
Bortezomib (Proteasome Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05250973 — Phase 2
~0 spots leftby Nov 2024
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