What side effects are associated with this type of intervention?

Common treatments for amyloidosis, particularly those involving Daratumumab (an anti-CD38 monoclonal antibody), often include combinations with cyclophosphamide, bortezomib, and dexamethasone. Known side effects of these treatments can include infusion reactions, increased risk of infections, peripheral sensory neuropathy, gastrointestinal disorders, fluid retention, fatigue, and fever. Specifically, Daratumumab-related side effects may also include lymphopenia and infusion reactions. These side effects should be carefully monitored and managed in clinical settings.

What prior FDA approvals exist?

Daratumumab, an anti-CD38 monoclonal antibody, has been studied and used in combination with other drugs for the treatment of Amyloidosis. Specifically, the combination of Daratumumab with Bortezomib, Melphalan, and Dexamethasone (D-VCd) has been explored for its efficacy and safety in treating newly diagnosed systemic amyloid light chain (AL) amyloidosis with cardiac involvement. This combination aims to improve patient outcomes by leveraging the synergistic effects of these drugs. Other related treatments include the use of Lenalidomide and Dexamethasone, which have also been studied for their effectiveness in AL amyloidosis. These combinations are part of ongoing efforts to enhance therapeutic strategies for this condition.

What other types of research exist?

Promising novel alternatives to Daratumumab for Amyloidosis patients include Isatuximab (another anti-CD38 monoclonal antibody) and Elotuzumab (an anti-SLAMF7 monoclonal antibody). Both have shown efficacy in multiple myeloma and are being explored for their potential in treating amyloidosis. Additionally, therapies targeting amyloid deposits directly, such as antibodies designed to dissolve existing amyloid deposits, are under study and may offer new treatment avenues.

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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.

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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 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

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%

Asthenia

15%

Insomnia

13%

Cough

11%

Nausea

11%

Pyrexia

11%

Dizziness

11%

Neuralgia

10%

Back Pain

10%

Pneumonia

10%

Back pain

10%

Neutropenia

Dyspnoea

Oedema peripheral

Oedema Peripheral

Hyperglycaemia

Pain in extremity

Pain in Extremity

Paraesthesia

Headache

Bronchitis

Arthralgia

Epistaxis

Bone pain

Bone Pain

Decreased Appetite

Dyspepsia

Leukopenia

Hypokalaemia

Decreased appetite

Hypocalcaemia

Lymphopenia

Oedema

Vomiting

Hypotension

Abdominal pain

Alanine aminotransferase increased

Nasopharyngitis

Alanine Aminotransferase Increased

Abdominal pain upper

Hypertension

Abdominal Pain Upper

Hypophosphataemia

Conjunctivitis

Rash

Influenza

Muscle Spasms

Musculoskeletal Chest Pain

Muscle spasms

Aspartate aminotransferase increased

Myalgia

Herpes zoster

Musculoskeletal chest pain

Urinary tract infection

Herpes Zoster

Weight decreased

Pulmonary Embolism

Nasal congestion

Weight Decreased

Pulmonary embolism

Myocardial infarction

Dehydration

Myocardial Infarction

Sepsis

Lower Respiratory Tract Infection

Abdominal Pain

Orthostatic Hypotension

General Physical Health Deterioration

Condition aggravated

General physical health deterioration

Hyponatraemia

Orthostatic hypotension

Syncope

Productive cough

Lower respiratory tract infection

Respiratory failure

Chills

Gastroenteritis

Respiratory Failure

Condition Aggravated

100%

80%

60%

40%

20%

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

Bortezomib

2005

Completed Phase 3

~1410

Dexamethasone

2007

Completed Phase 4

~2650

Daratumumab

2014

Completed Phase 3

~2380

Cyclophosphamide

2010

Completed Phase 4

~2310

0 / 4Eligibility criteria met

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.