What side effects are associated with this type of intervention?

Common treatments for amyloidosis, particularly those involving daratumumab (a monoclonal antibody targeting CD38), can have several side effects. Daratumumab-based regimens are associated with higher rates of infections, including pneumonia, and infusion reactions. Severe lymphocytopenia can lead to increased susceptibility to infections like Epstein-Barr virus, CMV reactivation, and fungal meningitis. Bortezomib can cause peripheral sensory neuropathy, gastrointestinal disorders, and fatigue. Cyclophosphamide may lead to cytopenias and increased infection risk, while dexamethasone can cause hyperglycemia, insomnia, and increased infection risk. These side effects necessitate careful monitoring and management during treatment.

What prior FDA approvals exist?

Daratumumab, a monoclonal antibody targeting CD38, has been studied for its efficacy in treating systemic amyloid light-chain (AL) amyloidosis. The FDA has approved Daratumumab for multiple myeloma, and its combination with other drugs like cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is being evaluated for AL amyloidosis. Other related treatments include lenalidomide and dexamethasone, which have shown activity in AL amyloidosis. These treatments aim to reduce the production of amyloidogenic light chains and improve patient outcomes.

What other types of research exist?

Promising novel alternatives to Daratumumab for Amyloidosis patients include Isatuximab, another anti-CD38 monoclonal antibody, and Elotuzumab, which targets SLAMF7. Both have shown efficacy in multiple myeloma and may offer potential benefits for Amyloidosis treatment.

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Proteasome Inhibitor

Daratumumab + CyBorD for Amyloidosis

Phase 3

Waitlist Available

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

One or more organs impacted by AL amyloidosis according to consensus guidelines

Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance

Must not have

- For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization

Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, >= 60 percent (%) plasma cells in the bone marrow, or hypercalcemia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2.4 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests if adding daratumumab to a standard treatment (CyBorD) helps newly diagnosed AL amyloidosis patients more than the standard treatment alone. Daratumumab boosts the immune system to attack harmful cells, while CyBorD fights the disease with a mix of medicines. Daratumumab has shown promising results in improving blood and organ responses in AL amyloidosis, leading to its integration into standard treatment regimens.

Who is the study for?

This trial is for adults with newly diagnosed systemic AL amyloidosis, which affects their organs. They must have measurable disease levels and be in a stable enough condition to participate (ECOG Performance Status 0-2). People can't join if they plan on having a stem cell transplant soon, have serious heart issues or infections like HIV or hepatitis B/C, severe neuropathy, or are being treated for multiple myeloma.

What is being tested?

The study tests the effectiveness and safety of adding Daratumumab to the CyBorD treatment regimen (Cyclophosphamide, Bortezomib, Dexamethasone) versus using CyBorD alone in patients who've just been diagnosed with AL amyloidosis.

What are the potential side effects?

Possible side effects include reactions at the injection site, blood disorders like anemia and low platelets, nerve damage that could cause numbness or pain in hands and feet (neuropathy), increased risk of infection due to immune suppression by drugs used in treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My AL amyloidosis has affected one or more of my organs.

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My diagnosis of amyloidosis was confirmed through specific tissue staining and microscopy techniques.

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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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One of my organs is affected by AL amyloidosis.

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I have AL amyloidosis with measurable disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not been hospitalized for heart failure issues in the last 4 weeks.

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I have been diagnosed with multiple myeloma showing symptoms like bone damage or high calcium levels.

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My heart failure is classified as severe or very severe.

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I haven't been hospitalized for heart issues or had heart surgery in the last 6 months.

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I have a history of serious heart rhythm problems but do not have a pacemaker or ICD, though I may need one.

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My blood pressure is usually below 90 mmHg, or I get dizzy standing up despite treatment.

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I have tested positive for hepatitis B or have had it in the past.

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I experience mild numbness or mild pain in my hands or feet.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2.4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2.4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2.4 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

Percentage of Participants With Overall Complete Hematologic Response (CHR)

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%

Pneumonia

10%

Back pain

10%

Neutropenia

Dyspnoea

Oedema peripheral

Oedema Peripheral

Pain in extremity

Hyperglycaemia

Pain in Extremity

Arthralgia

Headache

Paraesthesia

Bronchitis

Bone pain

Epistaxis

Bone Pain

Decreased Appetite

Hypocalcaemia

Dyspepsia

Leukopenia

Hypokalaemia

Decreased appetite

Lymphopenia

Oedema

Vomiting

Hypotension

Alanine aminotransferase increased

Abdominal pain

Nasopharyngitis

Alanine Aminotransferase Increased

Hypertension

Rash

Abdominal Pain Upper

Conjunctivitis

Hypophosphataemia

Abdominal pain upper

Influenza

Muscle Spasms

Musculoskeletal Chest Pain

Aspartate aminotransferase increased

Muscle spasms

Urinary tract infection

Myalgia

Herpes zoster

Musculoskeletal chest pain

Herpes Zoster

Pulmonary Embolism

Weight Decreased

Pulmonary embolism

Myocardial infarction

Dehydration

Myocardial Infarction

Lower Respiratory Tract Infection

Abdominal Pain

Orthostatic Hypotension

General Physical Health Deterioration

Condition aggravated

General physical health deterioration

Hyponatraemia

Orthostatic hypotension

Lower respiratory tract infection

Syncope

Productive cough

Nasal congestion

Respiratory failure

Weight decreased

Chills

Gastroenteritis

Sepsis

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.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: CyBorD plus DaratumumabExperimental Treatment1 Intervention

Participants will receive dexamethasone (20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing) followed by 1800 mg of daratumumab subcutaneously followed by cyclophosphamide (300 mg/m\^2 orally or IV dose weekly) and bortezomib (1.3 mg/m\^2 subcutaneous injection weekly) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 2 years.

Group II: CyBorD alone (cyclophosphamide/bortezomib/dexamethasone)Active Control3 Interventions

Participants will receive dexamethasone (40 milligrams \[mg\] orally or intravenous \[IV\] dose), followed by cyclophosphamide (300 milligram per meter square \[mg/m\^2\] orally or IV dose), then bortezomib (1.3 mg/m\^2 subcutaneous injection) weekly on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Daratumumab

2014

Completed Phase 3

~2000

0 / 13Eligibility 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

The most common treatments for Amyloidosis, such as Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone, work through different mechanisms to target the disease. Daratumumab is a monoclonal antibody that targets CD38 on plasma cells, leading to their destruction. 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 abnormal cells. Dexamethasone is a corticosteroid that reduces inflammation and suppresses immune responses. These mechanisms are crucial for Amyloidosis patients as they help reduce the production of amyloid proteins, alleviate symptoms, and improve organ function, ultimately enhancing patient outcomes.