Triple Therapy for Lymphoma

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

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

Compensation: Varies

Number of Visits: 4

Duration: 28 days per cycle

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of alisertib and bortezomib when given together with rituximab in treating patients with mantle cell lymphoma or B-cell low grade non-Hodgkin lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Alisertib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving alisertib and bortezomib together with rituximab may be a better treatment for relapsed or refractory mantle cell lymphoma or B-cell low grade non-Hodgkin lymphoma.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must stop using proton pump inhibitors at least 4 days before the first dose, and you cannot take them during the study. Other medications like H2 receptor antagonists, antacids, pancreatic enzymes, and certain antiepileptic drugs are also not allowed during the trial.

What data supports the effectiveness of the drug combination including Alisertib, MLN8237, Bortezomib, Velcade, Rituximab, Rituxan, Riabni, Ruxience, and Truxima for treating lymphoma?

Research shows that combining rituximab with other drugs like bortezomib can be effective in treating certain types of lymphoma, such as follicular lymphoma. Rituximab, a key component of this combination, has been shown to improve survival rates when added to chemotherapy for various lymphomas. ^{1 2 3 4 5}

Is the triple therapy for lymphoma safe for humans?

The research does not provide specific safety data for the triple therapy involving Alisertib, Bortezomib, and Rituximab for lymphoma, but it does mention that similar treatments for nausea and vomiting in chemotherapy are generally well tolerated with no serious adverse events. ^{6 7 8 9 10}

What makes the triple therapy for lymphoma unique?

The triple therapy for lymphoma combines Alisertib, Bortezomib, and Rituximab, which is unique because it integrates targeted therapies like Rituximab, a monoclonal antibody that targets CD20 on B-cells, with other agents like Bortezomib, a proteasome inhibitor, potentially enhancing treatment effectiveness by attacking the cancer cells through different mechanisms. ^{1 3 11 12 13}

Research Team

Catherine S Diefenbach

Principal Investigator

Montefiore Medical Center - Moses Campus

Eligibility Criteria

This trial is for adults with relapsed or refractory mantle cell lymphoma or low grade B-cell non-Hodgkin lymphoma. Participants must have adequate organ function, no high-grade cancer transformation, and agree to use contraception. They should not have had certain treatments recently and must be able to take oral medication.

Inclusion Criteria

My lymphoma can be measured or evaluated and I've had the necessary scans and tests recently.

Platelets >= 75,000/mcL or >= 50,000/mcL with documented bone marrow involvement (obtained within 30 days of registration)

My kidney function, measured by creatinine levels or clearance, is within the normal range.

Exclusion Criteria

I have had allergic reactions to medications similar to MLN8237, bortezomib, or rituximab.

You are not currently taking any other experimental medications.

I am not taking pancreatic enzymes while on this study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive alisertib orally twice daily on days 1-7, bortezomib subcutaneously on days 1, 8, and 15, and rituximab intravenously on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

3 visits per cycle (in-person)

Extended Treatment

After 8 courses, treatment with rituximab repeats once every 3 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.

12 weeks per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Alisertib
• Bortezomib
• Rituximab

Trial Overview The trial tests the combination of alisertib and bortezomib with rituximab to find the best dose and side effects profile in treating specific types of lymphoma that are resistant or have returned after treatment. It aims to see if this combo can better inhibit cancer cell growth.

Participant Groups

Group I: Treatment (alisertib, bortezomib, and rituximab) Experimental Treatment 4 Interventions

Patients receive alisertib PO BID on days 1-7; bortezomib SC on days 1, 8, and 15; and rituximab IV on day 1. Treatment repeats every 28 days\* in the absence of disease progression or unacceptable toxicity. Note: \*After 8 courses, treatment with rituximab repeats once every 3 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.

Alisertib is already approved in United States, European Union for the following indications:

Approved in United States as Alisertib for:

• Acute myeloid leukemia (AML)

Approved in European Union as Alisertib for:

• None approved; under investigation for various cancers

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Recent advances in targeted therapies for non-Hodgkin lymphoma, particularly the anti-CD20 monoclonal antibody rituximab, are expected to significantly improve patient care by inhibiting specific disease pathways.

Combining rituximab with other agents, such as monoclonal antibodies, immunomodulatory drugs, and Bcl-2 inhibitors, shows promise for enhancing treatment efficacy, especially in patients who do not respond to rituximab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies for non-Hodgkin lymphoma: rationally designed combinations. Martin, P., Leonard, JP.[2019]

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]

Rituximab has been shown to significantly improve progression-free and overall survival in patients with various types of non-Hodgkin lymphoma and chronic lymphocytic leukaemia (CLL), based on a systematic review of 56 randomized controlled trials.

The consensus guidelines recommend rituximab for use in combination with chemotherapy for initial treatment of aggressive B-cell lymphomas, maintenance therapy for indolent B-cell lymphomas, and as part of treatment regimens for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in Lymphoma and Chronic Lymphocytic Leukaemia: A Practice Guideline. Prica, A., Baldassarre, F., Hicks, LK., et al.[2018]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

Rituximab is the first FDA-approved monoclonal antibody for cancer treatment, specifically targeting the CD20 antigen on B cells, and has shown efficacy in treating relapsed low-grade and follicular non-Hodgkin's lymphoma in multicenter studies.

The treatment is generally well-tolerated, with side effects mainly consisting of mild fevers and chills during the first infusion, and its low immunogenicity allows for potential future treatments without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. Leget, GA., Czuczman, MS.[2019]

Rituximab has shown a response rate of approximately 70% as a first-line treatment for indolent lymphoma, with low toxicity and the ability to retreat patients successfully, leading to longer remission durations.

Combination therapies using rituximab with chemotherapy have resulted in high complete response rates and a greater likelihood of molecular complete remission compared to chemotherapy alone, indicating its potential to enhance treatment outcomes in lymphoid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy in lymphoid malignancies. Hainsworth, JD.[2019]

References

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

Targeted therapies for non-Hodgkin lymphoma: rationally designed combinations. [2019]

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

Rituximab: clinical development and future directions. [2019]

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

Rituximab in Lymphoma and Chronic Lymphocytic Leukaemia: A Practice Guideline. [2018]

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

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]

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

Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. [2020]

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

Efficacy and safety of triple therapy with aprepitant, ondansetron, and prednisone for preventing nausea and vomiting induced by R-CEOP or CEOP chemotherapy regimen for non-Hodgkin lymphoma: a phase 2 open-label, randomized comparative trial. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

A retrospective study of R-CHOP/CHOP therapy-induced nausea and vomiting in non-Hodgkin's lymphoma patients: a comparison of intravenous and oral 5-HT3 receptor antagonists. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Tropisetron in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Use of granisetron in patients refractory to previous treatment with antiemetics. [2019]

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

Comparative efficacy of oral and intravenous granisetron for the prevention of acute chemotherapy-induced emesis. [2019]

11. Japan pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. [2015]

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

Use of rituximab, the new FDA-approved antibody. [2019]

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

Monoclonal antibody therapy in lymphoid malignancies. [2019]