Ixazomib Maintenance for AL Amyloidosis

Recruiting at 8 trial locations

Overseen By Hani Hassoun, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Proteosome inhibitors

Must not be taking: Strong CYP3A inducers

Disqualifiers: Active infection, Cardiovascular conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 24 months

17 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications like strong CYP3A inducers (e.g., rifampin, carbamazepine) or St. John's wort within 14 days before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Ixazomib for AL Amyloidosis?

Research shows that the combination of ixazomib and dexamethasone improved the time before vital organ deterioration or death in patients with relapsed AL amyloidosis compared to other treatments. Additionally, ixazomib has shown a 52% response rate in patients with relapsed AL amyloidosis, indicating it can be effective in managing the condition. ^{1 2 3 4 5}

How is the drug ixazomib unique for treating AL amyloidosis?

Ixazomib is unique for treating AL amyloidosis because it is the first oral proteasome inhibitor (a type of drug that blocks the action of proteasomes, which are protein complexes that break down proteins) used in this condition, offering a convenient oral administration compared to other treatments that require injections or infusions. It has shown promising results in terms of hematologic response and progression-free survival, especially in patients with relapsed or refractory AL amyloidosis, and has a generally manageable safety profile. ^{1 3 4 5 6}

What is the purpose of this trial?

The purpose of this study is to learn if Ixazomib maintenance treatment (chemotherapy) works to control the disease. Through this study, the investigators hope to learn more about ways to prevent or delay relapse of AL Amyloidosis.

Research Team

Heather Landau, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with AL Amyloidosis who've had a partial response to initial therapy, have organ involvement, and are within 12 months of starting treatment. They must not have severe neuropathy or active infections, be pregnant or breastfeeding, or have other recent cancers. Men and women must follow specific contraception guidelines.

Inclusion Criteria

I am a woman following specific guidelines regarding menopause, birth control, and pregnancy tests.

My blood tests show significant markers for my disease.

My AL amyloidosis affects at least one organ, like my kidneys, heart, or liver.

Exclusion Criteria

I have a stomach or intestine condition that could affect how I absorb pills.

I am not pregnant or breastfeeding.

My condition did not improve with proteasome inhibitor treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ixazomib at a fixed dose of 4mg on days 1, 8, and 15 of a 28-day cycle, with optional dexamethasone if tolerated, for up to 24 cycles or until disease progression

24 months

3 visits per 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Dexamethasone
• Ixazomib

Trial Overview The study tests if Ixazomib can control AL Amyloidosis after initial therapy success. It's given as maintenance chemotherapy to prevent disease relapse. Patients will also receive Dexamethasone as part of the treatment regimen.

Participant Groups

Group I: ixazomib Experimental Treatment 2 Interventions

Enrolled patients will receive ixazomib at a fixed dose of 4mg on days 1, 8, and 15 of a 28-day cycle. Ixazomib will be given orally on days 1, 8, and 15 of a 28 day cycle. Dexamethasone 4mg-12mg will be allowed on days 1, 8, 15 if patients previously tolerated dexamethasone without issue. Treatment cycles will be repeated until disease progression for up to 24 cycles or until development of significant treatment-related toxicities.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Tufts Medical Center

Collaborator

Trials

264

Recruited

264,000+

Findings from Research

In a phase 3 study involving 168 patients with relapsed/refractory AL amyloidosis, ixazomib combined with dexamethasone showed a median time to vital organ deterioration or mortality of 34.8 months, significantly longer than the 26.1 months observed with physician's choice treatments, indicating a potential benefit in delaying disease progression.

Although ixazomib-dexamethasone did not significantly outperform physician's choice in hematologic response rates (53% vs 51%), it demonstrated a favorable safety profile with manageable adverse events, making it a promising option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. Dispenzieri, A., Kastritis, E., Wechalekar, AD., et al.[2022]

A milder schedule of high-dose dexamethasone (40 mg for 4 days every 21 days) was tested in 23 AL amyloidosis patients, resulting in a 35% response rate within a median of 4 months, indicating its potential effectiveness.

This treatment regimen was associated with minimal toxicity, suggesting it could be a suitable front-line therapy for patients who cannot undergo autologous stem cell transplantation and need a quick response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A modified high-dose dexamethasone regimen for primary systemic (AL) amyloidosis. Palladini, G., Anesi, E., Perfetti, V., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A modified high-dose dexamethasone regimen for primary systemic (AL) amyloidosis. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of the combination of bortezomib and dexamethasone in systemic AL amyloidosis. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light-chain amyloidosis. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis. [2023]