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Corticosteroid

Venetoclax + Ixazomib + Dexamethasone for AL Amyloidosis

Phase 1
Recruiting
Led By Michael A Rosenzweig
Research Sponsored by National Cancer Institute (NCI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Age >= 18 years
Measurable disease of AL amyloidosis as defined by at least one of the following: 1) serum or urine monoclonal protein >= 500 mg/dL by protein electrophoresis, or 2) serum free light chain >= 20 mg/L with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) >= 20 mg/L
Must not have
Patients with New York Heart Association classification III/IV. Patients with advanced cardiac amyloidosis, Mayo stage IIIB based on European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement with NT-Pro BNP > 8500 pg/mL (Wechalekar et al., 2013)
Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of MLN9708 (ixazomib citrate), including difficulty swallowing
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 2.5 years
Awards & highlights

Summary

This trial tests a combination of venetoclax, ixazomib citrate, and dexamethasone in patients with difficult-to-treat light chain amyloidosis. Venetoclax alone has shown promise in treating this condition, indicating its potential effectiveness and safety. The drugs work together to kill cancer cells and reduce inflammation.

Who is the study for?
Adults with relapsed or refractory light chain amyloidosis, specifically those who have a genetic change known as translocation t(11;14). They should be in relatively good health (ECOG <=2), not HIV positive unless undetectable viral load on therapy, and without major organ damage from multiple myeloma. Prior cancer treatments must be completed at certain intervals before joining.
What is being tested?
The trial is testing the combination of venetoclax, ixazomib citrate, and dexamethasone to find the safest dose with the fewest side effects for treating light chain amyloidosis that has returned or isn't responding to treatment. Venetoclax blocks proteins cancer cells need to survive, while ixazomib helps kill them and dexamethasone reduces inflammation.
What are the potential side effects?
Potential side effects include nausea, diarrhea, fatigue, risk of infection due to low blood counts, liver issues reflected by changes in blood tests results. There may also be risks related to heart function given the nature of amyloidosis affecting different organs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I am 18 years old or older.
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My AL amyloidosis shows through specific blood or urine tests.
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My bone marrow biopsy shows I have the t(11;14) genetic marker.
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I can take care of myself but might not be able to do heavy physical work.
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My AL amyloidosis is at a cardiac risk stage of I, II, or IIIa.
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My condition is confirmed AL amyloidosis needing treatment.
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I had hepatitis C but have been treated and cured.
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My kidneys work well enough, with a clearance rate of at least 15 mL/min.
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My hepatitis B virus load is undetectable with treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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My heart condition is severe, classified as NYHA III/IV or I have advanced cardiac amyloidosis.
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I have no stomach or intestine problems that affect how I absorb pills.
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I am not taking any strong or moderate drugs that affect enzyme activity.
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My cancer has spread to my brain or spinal cord.
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I have severe diarrhea.
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I am not pregnant or breastfeeding while considering treatment with MLN9708.
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I am allergic to venetoclax, ixazomib, or dexamethasone.
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I do not have any serious ongoing illnesses or recent heart issues.
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I have severe nerve pain or numbness.
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I have been treated with MLN9708 or venetoclax before.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 2.5 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2.5 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
Incidence of adverse events
Maximum tolerated dose
Recommended phase 2 dose (RP2D)
Secondary study objectives
Overall response rate (complete hematologic response)
Other study objectives
Expression of BCL-2, BCL-XL, BAX, BAK, BIM, NOXA, and MCL-1
Hematologic response rates
Immune profile in the peripheral blood
+1 more

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471
33%
Neutropenia
11%
SARS-CoV-2 test positive
11%
Sepsis
11%
Abdominal pain
11%
Pneumonia
11%
Rhinovirus infection
11%
COVID-19
11%
Gastroenteritis
11%
Pneumonia pseudomonal
11%
Electrocardiogram QT prolonged
11%
Anaemia
11%
Neutrophil count decreased
11%
Hypokalaemia
11%
Febrile neutropenia
11%
Supraventricular tachycardia
11%
Blood creatinine increased
11%
White blood cell count decreased
11%
Dermatitis
100%
80%
60%
40%
20%
0%
Study treatment Arm
Bendamustine + Rituximab Crossover Substudy
Venetoclax + Rituximab Re-Treatment Substudy
Venetoclax + Rituximab Main Study
Bendamustine + Rituximab Main Study

Trial Design

1Treatment groups
Experimental Treatment
Group I: Treatment (venetoclax, ixazomib citrate, dexamethasone)Experimental Treatment10 Interventions
Patients receive venetoclax PO QD on days 1-28, ixazomib citrate PO on days 1, 8 and 15, and dexamethasone PO on days 1, 8, 15 and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo x-ray imaging and abdominal ultrasound during screening. Patients undergo bone marrow biopsy and/or aspiration as well as blood sample collection throughout the study. Patients may undergo CT scans, and/or MRI, and/or PET scans throughout the study.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Dexamethasone
2007
Completed Phase 4
~2650
Biospecimen Collection
2004
Completed Phase 3
~2020
Bone Marrow Aspiration and Biopsy
2016
Completed Phase 1
~40
Computed Tomography
2017
Completed Phase 2
~2740
Ixazomib Citrate
2012
Completed Phase 3
~970
Magnetic Resonance Imaging
2017
Completed Phase 3
~1160
Positron Emission Tomography
2011
Completed Phase 2
~2200
Transabdominal Ultrasound
2020
N/A
~50
Venetoclax
2019
Completed Phase 3
~2200

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 AL Amyloidosis include BCL-2 inhibitors like venetoclax, proteasome inhibitors such as ixazomib citrate, and anti-inflammatory drugs like dexamethasone. BCL-2 inhibitors work by blocking the Bcl-2 protein, which is essential for cancer cell survival, thereby promoting cancer cell death. Proteasome inhibitors disrupt the degradation of proteins within cancer cells, leading to cell death and reduced amyloid production. Anti-inflammatory drugs like dexamethasone reduce inflammation and modulate the immune response, which can help manage symptoms and improve the efficacy of other treatments. These mechanisms are crucial for AL Amyloidosis patients as they target the underlying pathology of the disease, aiming to reduce amyloid deposits and improve organ function.
Daratumumab: A Review in Newly Diagnosed Systemic Light Chain Amyloidosis.Multiple myeloma with onset of pancreas involvement: A case report.Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens.

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,877 Previous Clinical Trials
41,012,927 Total Patients Enrolled
2 Trials studying AL Amyloidosis
349 Patients Enrolled for AL Amyloidosis
Michael A RosenzweigPrincipal InvestigatorCity of Hope Comprehensive Cancer Center LAO
3 Previous Clinical Trials
86 Total Patients Enrolled

Media Library

Dexamethasone (Corticosteroid) Clinical Trial Eligibility Overview. Trial Name: NCT04847453 — Phase 1
AL Amyloidosis Research Study Groups: Treatment (venetoclax, ixazomib citrate, dexamethasone)
AL Amyloidosis Clinical Trial 2023: Dexamethasone Highlights & Side Effects. Trial Name: NCT04847453 — Phase 1
Dexamethasone (Corticosteroid) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04847453 — Phase 1
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