Ixazomib Maintenance for AL Amyloidosis

Not currently recruiting at 8 trial locations
HL
HH
Overseen ByHani Hassoun, M.D.
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
Must be taking: Proteosome inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug Ixazomib to determine its effectiveness in controlling AL Amyloidosis, a condition characterized by the buildup of abnormal proteins in organs and tissues. The goal is to assess whether Ixazomib can prevent or delay the recurrence of the disease. Participants will receive Ixazomib along with Dexamethasone, if tolerated. The trial seeks individuals diagnosed with AL Amyloidosis who have undergone initial treatment and have at least one organ affected by the condition. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ixazomib, when combined with dexamethasone, is generally well-tolerated by patients with AL amyloidosis. In earlier studies, about 63% of patients taking this combination improved their condition. These studies also aimed to find the safest dose, and results suggest that most patients can handle the treatment well.

Although ixazomib is not yet specifically approved for AL amyloidosis, it has been studied in different contexts to better understand its safety. Patients in these studies experienced some side effects, but they were mostly mild and manageable. These findings provide some reassurance about the treatment's safety, but discussing any concerns with a doctor remains important.12345

Why are researchers excited about this possible treatment for AL Amyloidosis?

Researchers are excited about ixazomib for AL amyloidosis because it offers a new mechanism of action compared to the current standard treatments, which typically include chemotherapy and stem cell transplantation. Ixazomib is a proteasome inhibitor, which means it works by blocking the protein complexes that break down unneeded proteins in cells, potentially reducing the buildup of amyloid. This oral medication also provides a more convenient administration compared to the intravenous delivery of many traditional options. Additionally, its targeted approach may lead to fewer side effects and improved safety, making it a promising option for patients who may not tolerate existing treatments well.

What evidence suggests that Ixazomib might be an effective treatment for AL Amyloidosis?

Research has shown that ixazomib, which participants in this trial will receive, may help treat AL Amyloidosis. One study found that 63% of patients with newly diagnosed AL Amyloidosis had a positive blood response when treated with a combination that included ixazomib. Another study examined patients whose disease returned after treatment and found that ixazomib helped 52% achieve a positive blood response, with 56% experiencing improvements in organ function. On average, the disease took 14.8 months to worsen. After one year, 60% of patients showed no disease progression, and 85% remained alive. These results suggest that ixazomib could effectively manage the disease and slow its progression.12678

Who Is on the Research Team?

Heather J. Landau, MD - MSK Bone Marrow ...

Heather Landau, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.
See 8 more

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.
See 10 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: ixazomibExperimental Treatment2 Interventions

Find a Clinic Near You

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+

Published Research Related to This Trial

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

Citations

A randomized phase 3 study of ixazomib–dexamethasone ...In a phase 1/2 study in relapsed/refractory AL amyloidosis, ixazomib appeared active and well tolerated in 27 patients (10 of whom received ...
Phase 2 trial of ixazomib, cyclophosphamide, and ...Ixazomib, cyclophosphamide, and dexamethasone combination achieved hematologic response in 63% of newly diagnosed AL amyloidosis patients.
Treatment Patterns and Clinical Outcomes of Patients With ...Median progression-free survival (41.4 months), event-free survival (24.4 months), and time to next treatment (43.2 months) were unexpectedly ...
A phase 1/2 study of the oral proteasome inhibitor ixazomib in ...Median hematologic progression-free survival was 14.8 months; 1-year progression-free and overall survival rates were 60% and 85%, respectively (median follow- ...
A phase 1/2 study of the oral proteasome inhibitor ixazomib in ...Ixazomib is active in patients with relapsed/refractory AL amyloidosis with encouraging hematologic (52%) and organ (56%) response rates. Abstract. This phase 1 ...
Takeda Provides Update on TOURMALINE-AL1 Phase 3 ...There are currently no treatments approved for the treatment of AL amyloidosis. About NINLARO™ (ixazomib) capsules. NINLARO™ (ixazomib) is an oral proteasome ...
A phase I/II study to assess safety and dose of ixazomib in ...A phase I/II study to assess safety and dose of ixazomib in combination with cyclophosphamide and dexamethasone in newly diagnosed patients with light chain (AL) ...
Study Details | NCT03236792 | Ixazomib In Combination ...This is an open label multi-center, dose escalation safety study for patients with newly diagnosed AL Amyloidosis. A 3+3 design will be utilized to ...
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