Ixazomib + Rituximab for Non-Hodgkin Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: CYP1A2 inhibitors, CYP3A inhibitors

Disqualifiers: 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: 30

Duration: 6 months

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well ixazomib citrate and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that grows slowly (indolent). Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving ixazomib citrate together with rituximab may work better in treating indolent B-cell non-Hodgkin lymphoma.

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 strong inhibitors or inducers of specific enzymes (like some antibiotics and antifungals) within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is the combination of Ixazomib and Rituximab safe for humans?

Rituximab, used for conditions like non-Hodgkin's lymphoma and neuromyelitis optica, is generally safe but can cause side effects like neutropenia (low white blood cell count), especially after long-term use. These side effects are uncommon and often occur during the first infusion, but they usually resolve without treatment. ^{1 2 3 4 5}

How is the drug Ixazomib + Rituximab unique for treating non-Hodgkin lymphoma?

The combination of Ixazomib and Rituximab is unique because Ixazomib is a proteasome inhibitor that works by blocking the action of proteasomes (cellular complexes that break down proteins), which is different from Rituximab's mechanism of targeting the CD20 antigen on B-cells. This combination may offer a novel approach by using two different mechanisms to treat non-Hodgkin lymphoma. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Ixazomib for treating Non-Hodgkin Lymphoma?

Ixazomib has been shown to be effective in treating multiple myeloma, a type of blood cancer, by significantly prolonging the time patients live without their disease getting worse. It works by blocking a part of the cell that breaks down proteins, which can help kill cancer cells. ^{11 12 13 14 15}

Who Is on the Research Team?

Ajay K. Gopal

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with certain slow-growing B-cell non-Hodgkin lymphomas, who haven't had specific treatments before. Participants must be able to consent, have adequate organ function, and if of childbearing potential, agree to use effective contraception or practice abstinence. They should not have active infections or other serious health issues that could affect the study.

Inclusion Criteria

Your total bilirubin level is not more than 1.5 times the upper limit of the normal range.

Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

I have a tumor larger than 1.5 cm, high lymphocyte count, or measurable IgM in my blood.

Exclusion Criteria

I haven't needed antibiotics for an infection in the last 14 days.

I do not have an ongoing infection, hepatitis B or C, or HIV.

Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ixazomib citrate orally on days 1, 8, 15, and 22. Cycles repeat every 28 days for 6 cycles, followed by rituximab intravenously once weekly for 4 doses, then ixazomib citrate alone until disease progression or unacceptable toxicity.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Follow-up at 30 days, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ixazomib Citrate
• Rituximab

Trial Overview The trial tests ixazomib citrate combined with rituximab against indolent B-cell non-Hodgkin lymphoma. Ixazomib may block enzymes needed for cancer cell growth while rituximab might prevent cancer spread by targeting specific cells.

How Is the Trial Designed?

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

Patients receive ixazomib citrate orally (PO) on days 1, 8 ,15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Upon completion of 6 cycles of ixazomib citrate therapy, patients also receive rituximab intravenously (IV) once weekly for 4 doses total, followed by ixazomib citrate alone, until disease progression or unacceptable toxicity.

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

Approved in European Union as Ninlaro for:

• Multiple myeloma

Approved in United States as Ninlaro for:

• Multiple myeloma

Approved in Canada as Ninlaro for:

• Multiple myeloma

Approved in Japan as Ninlaro for:

• Multiple myeloma

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Millennium Pharmaceuticals, Inc.

Industry Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Published Research Related to This Trial

Ixazomib is an orally taken proteasome inhibitor that works by blocking the β5 subunit of the proteasome, and it was approved by the FDA in 2015 for treating multiple myeloma in combination with lenalidomide and dexamethasone after at least one prior therapy.

Currently, ixazomib is being studied in Phase III trials for newly diagnosed multiple myeloma and other conditions, indicating its potential for broader applications in treating various cancers and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: First Global Approval. Shirley, M.[2018]

Ixazomib, an oral proteasome inhibitor, significantly prolongs progression-free survival (PFS) in patients with relapsed and/or refractory multiple myeloma compared to placebo, as demonstrated in the TOURMALINE-MM1 trial involving adults who had received one to three prior therapies.

The treatment showed a favorable safety profile and resulted in a higher overall response rate, making ixazomib a valuable new option for patients with multiple myeloma who have undergone previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. Al-Salama, ZT., Garnock-Jones, KP., Scott, LJ.[2018]

In a study of 90 patients with relapsed/refractory multiple myeloma, the combination of ixazomib, thalidomide, and dexamethasone showed a 51.1% overall response rate, indicating significant efficacy in treating this condition.

The treatment was well tolerated, with rare occurrences of severe toxicities, and ixazomib maintenance therapy improved response depth in 12.4% of patients, suggesting a beneficial long-term effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. Ludwig, H., Poenisch, W., Knop, S., et al.[2021]

Ixazomib, an oral proteasome inhibitor, has been shown to significantly improve progression-free survival in patients with relapsed and/or refractory multiple myeloma when combined with lenalidomide and dexamethasone, with a median survival of 20.6 months compared to 14.7 months for the placebo group.

The drug works by selectively inhibiting the 20S proteasome, leading to the accumulation of proteins that induce stress and apoptosis in myeloma cells, making it a promising treatment option for patients who have undergone prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. Machida, M., Fukunaga, S., Hara, T.[2019]

Rituximab significantly reduces the annualized relapse rates in patients with relapsing-remitting multiple sclerosis, with a decrease of 0.80 relapses per year based on a meta-analysis of 15 studies involving 946 patients.

The treatment is well tolerated, with only mild-to-moderate adverse events occurring in 29.6% of patients and no severe adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis. Hu, Y., Nie, H., Yu, HH., et al.[2019]

Ibritumomab tiuxetan radioimmunotherapy demonstrated a 74% overall response rate in patients with rituximab-refractory follicular non-Hodgkin's lymphoma, indicating its efficacy as a treatment option for this difficult-to-treat population.

The treatment was well-tolerated with acceptable safety, as radiation doses to healthy organs were below safety limits, although it did lead to significant hematologic adverse events, including grade 4 neutropenia in 35% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. Witzig, TE., Flinn, IW., Gordon, LI., et al.[2022]

In a phase II study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

Rituximab was the first monoclonal antibody approved for cancer therapy and has significantly improved survival rates in patients with diffuse large cell lymphoma when combined with CHOP chemotherapy.

Initially approved in 1997 for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma, rituximab is also being researched for other B-cell malignancies and nonmalignant diseases like autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. King, KM., Younes, A.[2015]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ixazomib: First Global Approval. [2018]

2. France pubmed.ncbi.nlm.nih.gov

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. [2019]

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

A meta-analysis on efficacy and safety of rituximab for neuromyelitis optica spectrum disorders. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Late-onset neutropenia during long-term rituximab therapy in neuromyelitis optica. [2015]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis. [2019]

9. France pubmed.ncbi.nlm.nih.gov

[Monoclonal antibody therapy for non-Hodgkin's lymphoma]. [2016]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Rituximab at lower dose for neuromyelitis optica spectrum disorder: a multicenter, open-label, self-controlled, prospective follow-up study. [2023]

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

Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. [2015]

14. England pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. [2015]

15. England pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. [2019]