Immunotherapy for Hodgkin's Lymphoma

Recruiting at 34 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: Classical Hodgkin lymphoma, CNS involvement, 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: 6

Duration: 8-16 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new treatment called mosunetuzumab against the usual treatment, rituximab, for patients with a type of cancer called NLPHL. Both treatments help the immune system find and kill cancer cells by targeting a specific protein on these cells. The goal is to see if mosunetuzumab can improve survival better than rituximab.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic immunosuppressive medications within 2 weeks before starting the study treatment.

What safety information is available for immunotherapy treatments like Rituximab and similar drugs?

Rituximab, a type of immunotherapy, has been used for over 10 years and is generally safe, but it can increase the risk of infections, especially in people with weakened immune systems. Common side effects of monoclonal antibodies like Rituximab include flu-like symptoms during the first infusion, and there is a risk of serious infections like hepatitis B reactivation and a rare brain infection called PML. ^{1 2 3 4 5}

How is the drug Mosunetuzumab, Rituximab unique for treating Hodgkin's Lymphoma?

Mosunetuzumab is a novel drug that works by engaging the body's immune system to target and destroy cancer cells, while Rituximab is a well-established antibody that targets a specific protein on B cells. This combination may offer a new approach for treating Hodgkin's Lymphoma by potentially enhancing the immune response against the cancer. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Rituximab for treating Hodgkin's Lymphoma?

Rituximab has shown effectiveness in treating certain types of non-Hodgkin's lymphoma and has been used in combination with other treatments for relapsed and refractory Hodgkin lymphoma, suggesting potential benefits in similar conditions. ^{6 7 11 12 13}

Who Is on the Research Team?

Raphael Steiner, MD

Principal Investigator

University of Texas MD Anderson Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), either untreated or previously treated but not within the last 6 months if rituximab was used. Participants need to have symptoms like fever, weight loss, night sweats, or measurable disease and can't just be observed. They must also have good organ function and performance status.

Inclusion Criteria

Patients must have measurable disease according to the Lugano/LYRIC classification

Agreement to use adequate contraception by women of childbearing potential and men

Ability to understand and sign a written informed consent document

Exclusion Criteria

Uncontrolled intercurrent illness or significant conditions making participation hazardous

I have or might have a long-term EBV or CMV infection.

I have not had infections needing IV treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either mosunetuzumab or rituximab. Mosunetuzumab is administered subcutaneously on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles, repeating every 21 days for up to 8 cycles. Rituximab is administered intravenously on day 1 and with hyaluronidase human subcutaneously on days 8, 15, and 22 of each cycle, repeating every 28 days for up to 2 cycles.

8-16 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for 2 years.

2 years

Follow-up visits every 6 months

Crossover

Participants experiencing disease progression may crossover to the alternate treatment arm at week 12.

Until disease progression or unacceptable toxicity

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Rituximab

Trial Overview The study compares mosunetuzumab with the usual treatment of rituximab in improving survival for NLPHL patients. Both drugs are monoclonal antibodies targeting CD20 on B cells and cancer cells, potentially helping the immune system destroy these cells.

How Is the Trial Designed?

Group I: Arm I (Mosunetuzumab) Experimental Treatment 7 Interventions

Patients receive mosunetuzumab SC on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience PD will be permitted to crossover to arm II at week 12. Patients also receive FDG and undergo PET/CT at baseline and end of treatment. Patients who are positive at pre-treatment bone marrow biopsy also receive FDG and undergo PET/CT on study. Patients also undergo bone marrow biopsy and tissue biopsy at baseline, and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and tissue biopsy at end of treatment.

Group II: Arm II (Rituximab, Rituximab and hyaluronidase human) Active Control 8 Interventions

Patients receive rituximab IV on day 1 and rituximab and hyaluronidase human SC on days 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 2 cycles 8 weeks apart in the absence of disease progression or unacceptable toxicity. Patients may receive rituximab IV on days 8, 15, and 22 of each cycle if rituximab and hyaluronidase human is not available. Patients who experience PD will be permitted to crossover to arm I at week 12. Patients also receive FDG and undergo PET/CT at baseline and end of treatment. Patients who are positive at pre-treatment bone marrow biopsy also receive FDG and undergo PET/CT on study. Patients also undergo bone marrow biopsy and tissue biopsy at baseline, and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and tissue biopsy at end of treatment.

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

Approved in European Union as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in United States as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A 45-year-old woman with a history of Hodgkin's disease transformed into high-grade non-Hodgkin's lymphoma was successfully treated with Rituximab, a CD20 antibody, achieving complete remission 14 months later.

This case suggests that Rituximab can be an effective immunotherapy option for patients with chemotherapy-resistant cases of lymphoma, highlighting its potential in treating related lymphomas due to the clonal relationship between Hodgkin's disease and non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transformation of Hodgkin's disease to high-grade B-cell lymphoma: remission after Rituximab monotherapy. Kirchner, EM., Ebsen, M., Kirchner, J., et al.[2020]

In a study of 7 patients with relapsed and refractory Hodgkin lymphoma, Rituximab combined with second-line chemotherapy regimens led to a complete remission in 4 patients, demonstrating its efficacy as a treatment option.

The two-year survival rate was 85.7%, although the treatment was associated with significant side effects, particularly bone marrow suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rituximab combined with second line regimens for treatment of seven relapsed and refractory Hodgkin lymphoma patients]. Liu, H., Li, H., Xiong, W., et al.[2020]

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 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]

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]

Rituximab has significantly improved survival rates in patients with non-Hodgkin lymphomas, but there is a lack of comprehensive data on its long-term safety, indicating a need for extended patient follow-up.

Current literature provides limited guidance on systematic follow-up models for patients receiving rituximab, highlighting the necessity for developing monitoring strategies to ensure patient safety and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? Hegele, V., Stoll, P., Wüst, D., et al.[2021]

Brentuximab vedotin, a targeted therapy for Hodgkin lymphoma, is effective for patients at high risk of recurrence or relapse, but it can cause significant side effects, particularly peripheral neuropathy.

For patients who relapse after brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) is an option, though it carries unpredictable immune-related side effects, highlighting the need for careful management in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. Michot, JM., Lazarovici, J.[2023]

Monoclonal antibodies (MoAbs) like rituximab, trastuzumab, and alemtuzumab have revolutionized targeted cancer therapy since their introduction, offering different adverse event profiles compared to traditional chemotherapy.

The most common side effects of MoAbs are infusion-related reactions, which can include flu-like symptoms and severe reactions like hypotension and bronchospasm, primarily occurring during the first infusion and manageable by adjusting the infusion rate and using medications to alleviate symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unique aspects of supportive care using monoclonal antibodies in cancer treatment. Dillman, RO., Hendrix, CS.[2020]

In a review of 49,927 reports from the Spanish Pharmacovigilance System, rituximab was associated with common adverse reactions such as white cell disorders, hypotension, dyspnoea, and pneumonitis, with white cell disorders typically developing around 21 days after treatment.

Trastuzumab was primarily linked to cardiac failure, with many cases occurring alongside other medications, reinforcing the known safety profiles of both drugs as consistent with findings from large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab. González, V., Salgueiro, E., Jimeno, FJ., et al.[2015]

Rituximab has been shown to be very safe over more than 10 years of use, but it can significantly increase the risk of infections, especially in patients with low-grade lymphoma or severe immunodeficiency, such as those with HIV or on immunosuppressive therapies.

The most critical infection associated with rituximab is hepatitis B reactivation, which can lead to severe liver failure; therefore, screening for hepatitis B and considering preemptive antiviral treatment is essential for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-associated infections. Gea-Banacloche, JC.[2020]

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, an anti-CD20 antibody, has been shown to be effective in treating various B-cell lymphoid malignancies, with benefits including improved response rates and progression-free survival, based on extensive clinical data since its introduction in 1997.

The drug is generally well-tolerated, with infusion-related side effects being the most significant, and its use has expanded from treating relapsed low-grade lymphomas to first-line therapy and more aggressive forms like diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. Collins-Burow, B., Santos, ES.[2015]

Rituximab, a chimeric monoclonal anti-CD20 antibody, shows enhanced effectiveness when combined with interferon alpha, leading to higher complete response rates and longer response durations in treatment.

While other immunomodulatory agents like interleukin-2 and Epratuzumab show potential for synergy with Rituximab, further randomized trials are needed to confirm their efficacy compared to Rituximab alone, particularly in indolent lymphomas where chemotherapy might be unnecessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of anti-CD20 monoclonal antibody in association with immunomodulatory agents]. Bosly, A.[2017]

Citations

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

Transformation of Hodgkin's disease to high-grade B-cell lymphoma: remission after Rituximab monotherapy. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[Rituximab combined with second line regimens for treatment of seven relapsed and refractory Hodgkin lymphoma patients]. [2020]

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

Rituximab: clinical development and future directions. [2019]

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

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

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? [2021]

7. France pubmed.ncbi.nlm.nih.gov

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023]

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

Unique aspects of supportive care using monoclonal antibodies in cancer treatment. [2020]

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

Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab. [2015]

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

Rituximab-associated infections. [2020]

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

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

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

Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. [2015]

13. France pubmed.ncbi.nlm.nih.gov

[Role of anti-CD20 monoclonal antibody in association with immunomodulatory agents]. [2017]