Immunotherapy for Lymphoma

Overseen By Stephen Smith

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: CD20 antibodies

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active infection, Autoimmune disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well pembrolizumab with rituximab or obinutuzumab work in treating patients with follicular lymphoma or diffuse large B cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Rituximab and obinutuzumab are monoclonal antibodies. They bind to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving pembrolizumab with rituximab or obinutuzumab may help kill more cancer cells in patients with follicular lymphoma or diffuse large B cell lymphoma.

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 participate if you are on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the trial, except for certain hormone replacement therapies.

Is immunotherapy for lymphoma generally safe for humans?

Obinutuzumab, used in various lymphoma treatments, generally has a manageable safety profile. Common side effects include mild to moderate infusion-related reactions (like fever or chills during the drug infusion) and neutropenia (a drop in white blood cells that can increase infection risk). Serious side effects are less common, and the safety profile is consistent with current risk management strategies. ^{1 2 3 4 5}

What makes the drug combination of Obinutuzumab, Pembrolizumab, and Rituximab unique for treating lymphoma?

This drug combination is unique because it includes Obinutuzumab, a novel anti-CD20 monoclonal antibody, which has shown effectiveness in patients who do not respond to or relapse after Rituximab treatment. Obinutuzumab is engineered to improve the immune system's ability to target and destroy cancer cells, offering a new option for those with limited responses to existing therapies. ^{1 6 7 8 9}

What data supports the effectiveness of the drug Obinutuzumab for treating lymphoma?

Obinutuzumab has shown effectiveness in treating follicular lymphoma, especially in patients who did not respond to or relapsed after rituximab treatment. In a large study, it significantly prolonged the time patients lived without the disease getting worse compared to another treatment, and it also improved overall survival for these patients. ^{1 7 10 11 12}

Who Is on the Research Team?

Stephen Smith

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory follicular lymphoma or diffuse large B cell lymphoma. They must have tried certain treatments like CD20 antibody therapy, not be eligible for high-dose chemotherapy and stem cell transplant, and lack better treatment options. Participants need a minimum hemoglobin level, measurable disease, good performance status (able to carry out daily activities), adequate organ function, and agree to use contraception.

Inclusion Criteria

My DLBCL has returned or I can't have high-dose chemo and stem cell transplant.

Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 X ULN (within 28 days of cycle 1 day 1)

Be willing and able to provide written informed consent/assent for the trial

Exclusion Criteria

Hypersensitivity to pembrolizumab or any of its excipients

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

I have or had lung inflammation not caused by an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive pembrolizumab and either rituximab or obinutuzumab. Treatment repeats every 3 weeks for 4 cycles.

12 weeks

4 visits (in-person)

Extended Therapy

Patients with at least a partial response receive pembrolizumab every 3 weeks for up to 2 years. Obinutuzumab may be given on specific cycles.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab
• Pembrolizumab
• Rituximab

Trial Overview The study tests pembrolizumab combined with either rituximab or obinutuzumab in patients whose lymphoma has returned after treatment or hasn't responded to previous therapies. Pembrolizumab is an immunotherapy drug that may help the immune system attack cancer cells; rituximab and obinutuzumab are antibodies targeting specific proteins on cancer cells.

How Is the Trial Designed?

Group I: Arm III (pembrolizumab, obinutuzumab) Experimental Treatment 3 Interventions

INDUCTION: Patients diagnosed with R/R FL receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab IV on days 1, 8, and 15 of cycle 1, and on day 1 of cycle 2. EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years (35 cycles) in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (pembrolizumab, rituximab) Experimental Treatment 3 Interventions

INDUCTION: Patients diagnosed with R/R DLBCL receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, and 15 of cycle 1, and on day 1 of cycle 2. EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years (35 cycles) in the absence of disease progression or unacceptable toxicity.

Group III: Arm I (pembrolizumab, rituximab) Experimental Treatment 3 Interventions

INDUCTION: Patients diagnosed with R/R FL receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, and 15 of cycle 1, and on day 1 of cycle 2. EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years (35 cycles) in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Approved in European Union as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Obinutuzumab, combined with bendamustine, significantly prolonged progression-free survival (PFS) in patients with indolent non-Hodgkin's lymphoma, particularly benefiting those with follicular lymphoma, as shown in the phase III GADOLIN study.

The treatment was generally well-tolerated, with mild to moderate infusion-related reactions being the most common side effects, while neutropenia was the most frequent severe adverse event, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. Dhillon, S.[2018]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

The Phase IIIb GREEN trial demonstrated that obinutuzumab (GA101) has a manageable toxicity profile in both first-line and relapsed/refractory chronic lymphocytic leukaemia (CLL) patients, with no new safety signals identified in the final analysis involving 630 first-line and 341 relapsed/refractory patients.

Common serious adverse events included neutropenia and thrombocytopenia, but the safety profile remained consistent with existing risk management strategies, while efficacy analyses indicated that certain treatment combinations, like obinutuzumab with fludarabine and cyclophosphamide, may lead to better outcomes in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of obinutuzumab alone or with chemotherapy in previously untreated or relapsed/refractory chronic lymphocytic leukaemia patients: Final analysis of the Phase IIIb GREEN study. Stilgenbauer, S., Bosch, F., Ilhan, O., et al.[2021]

In a study of 56 patients with relapsed/refractory follicular lymphoma, obinutuzumab combined with chemotherapy (either G-CHOP or G-FC) resulted in high response rates of 93% to 96%, indicating strong efficacy for this treatment approach.

The safety profile was acceptable, with most adverse events being mild infusion-related reactions; however, G-FC was associated with more adverse events compared to G-CHOP, suggesting that while both regimens are effective, G-CHOP may be better tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Radford, J., Davies, A., Cartron, G., et al.[2022]

Obinutuzumab (GA101) is an effective treatment for non-Hodgkin's lymphoma and is currently undergoing phase 3 clinical trials to further evaluate its efficacy.

A case report of a 62-year-old patient revealed a significant side effect, a widespread lichenoid eruption, highlighting the need for further investigation into the safety profile of GA101.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GA101 (a Novel Anti-CD20 Monoclonal Antibody)-Induced Lichenoid Eruption. Bakkour, W., Coulson, IH.[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]

Citations

1. France pubmed.ncbi.nlm.nih.gov

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. [2018]

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

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]

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

Obinutuzumab for B-cell malignancies. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Comparative analysis of rituximab or obinutuzumab combined with CHOP in first-line treatment of follicular lymphoma. [2023]

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

Durable complete responses from therapy with combined epratuzumab and rituximab: final results from an international multicenter, phase 2 study in recurrent, indolent, non-Hodgkin lymphoma. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of obinutuzumab alone or with chemotherapy in previously untreated or relapsed/refractory chronic lymphocytic leukaemia patients: Final analysis of the Phase IIIb GREEN study. [2021]

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

Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). [2022]

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

Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Rituximab versus obinutuzumab-based first-line chemoimmunotherapy for follicular lymphoma-a real-world multicenter retrospective cohort study. [2023]

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

GA101 (a Novel Anti-CD20 Monoclonal Antibody)-Induced Lichenoid Eruption. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Combined effects of histone deacetylase inhibitor and rituximab on non-Hodgkin's B-lymphoma cells apoptosis. [2015]

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]