Ixazomib + Rituximab for Mantle Cell Lymphoma

Overseen By Hun J Lee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Strong CYP3A inducers

Disqualifiers: Pregnancy, CNS involvement, Cardiovascular, 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: 12

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining ixazomib, a cancer drug, with rituximab for individuals with mantle cell lymphoma, a type of blood cancer. The focus is on patients whose cancer has returned or isn't responding to other treatments. Ixazomib may inhibit cancer cell growth by blocking certain enzymes, while rituximab could enhance the immune system's ability to attack cancer cells. This trial may suit those with mantle cell lymphoma that hasn't responded to at least two previous treatments, such as specific chemotherapy drugs and BTK inhibitors. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

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) 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 ixazomib and rituximab are likely to be safe for humans?

Research shows that patients generally tolerate the combination of ixazomib and rituximab well. Studies on patients with untreated indolent non-Hodgkin lymphoma (iNHL) have found this combination to be both effective and safe. In these studies, patients did not encounter major issues, and the treatment helped maintain strong immune systems.

Ixazomib and rituximab have also been tested together in patients with mantle cell lymphoma, a cancer type that can return or resist other treatments. The safety results so far are promising, indicating that patients can undergo the treatment without severe side effects.

Overall, while any treatment carries some risks, ixazomib and rituximab have demonstrated a good safety record in studies. Participants should still discuss any concerns with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ixazomib and rituximab for treating mantle cell lymphoma because it introduces a novel approach to tackling the disease. Unlike standard treatments that typically involve chemotherapy, ixazomib is a proteasome inhibitor that works by disrupting the protein breakdown process in cancer cells, causing them to die. This oral medication, combined with rituximab, an antibody therapy that targets specific proteins on cancer cells, offers a potentially more targeted and less toxic alternative. This combination could provide a more effective treatment with fewer side effects, making it a promising option for patients with this type of lymphoma.

What evidence suggests that ixazomib and rituximab might be an effective treatment for mantle cell lymphoma?

This trial will evaluate the combination of ixazomib and rituximab for treating mantle cell lymphoma. Studies have shown that this combination looks promising, especially when other treatments have failed. Research indicates that ixazomib can stop cancer cells from growing by blocking certain necessary enzymes. Rituximab aids the immune system in preventing tumor cells from spreading. Together, these drugs may work better than rituximab alone. Data from previous studies show that this combination is both effective and well-tolerated, suggesting it could be a strong option for patients whose mantle cell lymphoma has returned or hasn't responded to other treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Hun Lee, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with mantle cell lymphoma that's returned or isn't responding to BTK inhibitors. They need measurable disease, decent organ function (specific blood counts and liver/kidney tests), and a performance status of 0-2, indicating they can care for themselves. Women must not be pregnant and agree to contraception; men also need to use birth control.

Inclusion Criteria

Creatinine clearance >= 30 mL/min

Platelets >= 50,000/mm^3

Total bilirubin < 1.5 x institutional upper limit of normal (ULN). In patients with documented Gilbert's syndrome, total bilirubin =< 2.5 x ULN

Exclusion Criteria

I haven't taken specific strong medications or St. John's wort in the last 14 days.

Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial

I haven't had radiotherapy in the last 14 days, or if it was a small area, in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ixazomib orally on days 1, 8, and 15, and rituximab intravenously on days 1, 8, 15, and 22 of cycle 1. Treatment repeats every 28 days for up to 12 cycles.

48 weeks

12 cycles with multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Extension

Participants benefiting from treatment may continue to receive ixazomib indefinitely in the absence of disease progression or unacceptable toxicity.

What Are the Treatments Tested in This Trial?

Interventions

• Ixazomib
• Rituximab

Trial Overview The study is testing the combination of ixazomib, an enzyme blocker that may stop cancer growth, with rituximab, an immunotherapy drug that might prevent tumor cells from growing. The goal is to see if this combo works better than rituximab alone in patients who've had at least two prior treatments including chemotherapy and a BTK inhibitor.

How Is the Trial Designed?

Group I: Treatment (ixazomib, rituximab) Experimental Treatment 3 Interventions

Patients receive ixazomib by mouth on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of cycle 1. Beginning in cycle 3, patients receive rituximab Intravenous over 4-8 hours on day 1. Treatment repeats every 28 days up to cycle 12 in the absence of disease progression or unacceptable toxicity. Patients benefiting from treatment may continue to receive ixazomib indefinitely in the absence of disease progression or unacceptable toxicity.

Ixazomib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Ninlaro for:

• Multiple myeloma in combination with lenalidomide and dexamethasone

Approved in European Union as Ninlaro for:

• Multiple myeloma in combination with lenalidomide and dexamethasone

Approved in Canada as Ninlaro for:

• Multiple myeloma in combination with lenalidomide and dexamethasone

Approved in Japan as Ninlaro for:

• Multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36180329/

Ixazomib With or Without Rituximab Following ... During recruitment, published phase III data reported a survival benefit with rituximab maintenance, so all subsequent patients received ixazomib 4 mg at the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04047797?term=BI%20695500&viewType=Table&rank=7&tab=results

Study Results | Ixazomib and Rituximab in Treating ... These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable. Describes trials without FDA-defined phases ...

3. ashpublications.org ashpublications.org/bloodadvances/article-abstract/7/5/687/493245

Efficacy, safety, and molecular response predictors of oral ... For untreated iNHL, oral weekly ixazomib alone and with rituximab is effective, tolerated, and permits retention of immune competence. Subjects:.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265022002725

Ixazomib With or Without Rituximab Following ... During recruitment, published phase III data reported a survival benefit with rituximab maintenance, so all subsequent patients received ixazomib 4 mg at the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04047797

Ixazomib and Rituximab in Treating Patients With ... Giving ixazomib and rituximab may work better in treating patients with mantle cell lymphoma compared to rituximab alone. Detailed Description. PRIMARY ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9984960/

Efficacy, safety, and molecular response predictors of oral ... For untreated iNHL, oral weekly ixazomib alone and with rituximab is effective, tolerated, and permits retention of immune competence.

7. targetedonc.com targetedonc.com/view/study-underway-to-evaluate-ixazomib-rituximab-in-r-r-mcl

Study Underway to Evaluate Ixazomib/Rituximab in R/R MCL A study at MD Anderson Cancer Center aims to evaluate ixazomib and rituximab in patients with relapsed or refractory mantle cell lymphoma.