Obinutuzumab-Based Therapy for Follicular Lymphoma

Not currently recruiting at 515 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals, Aspirin

Must not be taking: PI3K inhibitors, Lenalidomide

Disqualifiers: CNS involvement, Prior PI3K, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6-12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of different treatment combinations for individuals with follicular lymphoma that has recurred or is unresponsive to treatment. It examines the effects of obinutuzumab (Gazyva), alone or with other drugs like umbralisib, lenalidomide, or chemotherapy. These treatments aim to boost the immune system to fight cancer or directly inhibit cancer cell growth and spread. Suitable candidates for this trial have follicular lymphoma that returned within two years after their first chemotherapy round and have undergone no more than one previous chemotherapy course. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain HIV medications or have had prior treatment with PI3K inhibitors or lenalidomide, you may not be eligible. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this trial have varying safety levels. Obinutuzumab, a type of immunotherapy, often causes infusion reactions, with 72% of patients experiencing reactions of varying severity. There is also a risk of Hepatitis B reactivation, which can lead to serious liver problems.

Umbralisib, used with obinutuzumab in one part of the trial, has raised safety concerns. The FDA withdrew its approval due to these concerns, indicating potential risks for patients.

In contrast, the combination of obinutuzumab and lenalidomide has shown promising safety results. Studies suggest this combination is generally well-tolerated and effective for patients with certain types of non-Hodgkin lymphoma, including follicular lymphoma.

However, when obinutuzumab is combined with bendamustine, important safety considerations arise. Some patients have experienced serious infections, with some linked to the treatment. This combination also carries risks of liver issues due to Hepatitis B reactivation.

Therefore, while some treatments in this trial have been considered safe in previous studies, others have known safety concerns that should be carefully considered when deciding whether to participate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for follicular lymphoma because they each offer a unique approach compared to standard options like R-CHOP, R-CVP, or bendamustine with rituximab. Obinutuzumab, for instance, is a monoclonal antibody similar to rituximab but with modifications that enhance its ability to target and destroy cancer cells. The combination of obinutuzumab with lenalidomide is noteworthy because lenalidomide boosts the immune system to fight cancer, offering a new angle by pairing it with an advanced antibody. Meanwhile, the obinutuzumab and umbralisib duo was promising because umbralisib is a PI3K inhibitor that targets cancer cell growth pathways, providing a different mechanism to tackle the disease. These innovative combinations are designed to improve treatment responses and potentially offer better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research shows that treatments using obinutuzumab hold promise for follicular lymphoma. In this trial, participants may receive obinutuzumab combined with lenalidomide. Studies have found that this combination results in 93.3% of patients not experiencing cancer progression over two years. Another trial arm involves obinutuzumab with bendamustine, which demonstrated strong results, with about 81.9% of patients remaining stable over three years. Although less information exists on obinutuzumab with umbralisib, which was part of a closed arm, obinutuzumab generally helps patients remain cancer-free longer. These treatments target cancer cells to stop their growth and spread, showing potential for treating follicular lymphoma that has returned or not responded to previous treatments. ^{3 6 7 8 9}

Who Is on the Research Team?

Paul M Barr

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with grade I-IIIa follicular lymphoma that has relapsed or is refractory. Eligible participants must have had only one prior chemotherapy regimen, be at least 18 years old, and have adequate organ function. They should not have CNS involvement by lymphoma or previous treatment with PI3K inhibitors or lenalidomide.

Inclusion Criteria

Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (=< 5 x IULN if secondary to lymphoma, Gilbert's syndrome, or medication related [e.g., indinavir, tenofovir, atazanavir]) within 28 days prior to registration

I have received anti-CD20 antibody therapy before CHOP or bendamustine treatment.

I've had one round of chemotherapy with CHOP or bendamustine.

Exclusion Criteria

I have never been treated with PI3K inhibitors or lenalidomide.

My lymphoma has not spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy for up to 12 cycles

6-12 months

Monthly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine Hydrochloride
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Lenalidomide
• Obinutuzumab
• Prednisone
• Umbralisib
• Vincristine Sulfate

Trial Overview The study tests obinutuzumab alone or combined with umbralisib, lenalidomide, or other chemotherapies to see which works best for treating relapsed/refractory follicular lymphoma. It explores how these treatments affect the immune system's ability to fight cancer and stop tumor growth.

How Is the Trial Designed?

Group I: Arm II (obinutuzumab, lenalidomide) Experimental Treatment 8 Interventions

Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.

Group II: Arm I (obinutuzumab, umbralisib) Experimental Treatment 8 Interventions

CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.

Group III: Arm III (obinutuzumab, combination chemotherapy) Active Control 12 Interventions

PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Obinutuzumab (G) combined with chemotherapy (G + Chemo) is shown to be a cost-effective treatment for previously untreated follicular lymphoma (FL) in Japan, with incremental cost-effectiveness ratios (ICERs) below the acceptable threshold of 7.5 million JPY per quality-adjusted life year (QALY).

The study found that the lowest lifetime direct medical costs were associated with the R-bendamustine (R-B) treatment group, primarily due to reduced hospitalization costs, highlighting the impact of treatment settings on overall expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. Ohno, S., Shoji, A., Hatake, K., et al.[2021]

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]

Obinutuzumab is an effective treatment for B-cell malignancies, specifically approved in the US for chronic lymphocytic leukaemia (CLL) in combination with chlorambucil, showcasing its efficacy in targeting cancer cells.

Utilizing GlycoMAb® technology, obinutuzumab enhances immune-mediated cell death through increased antibody-dependent cellular cytotoxicity, making it a promising option in ongoing phase III trials for various B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: first global approval. Cameron, F., McCormack, PL.[2021]

In the phase III GALLIUM trial involving 1202 patients with previously untreated follicular lymphoma, obinutuzumab-based immunochemotherapy significantly improved progression-free survival (PFS) compared to rituximab-based therapy, with 7-year PFS rates of 63.4% versus 55.7%.

While both treatments had similar overall survival rates (88.5% for obinutuzumab vs. 87.2% for rituximab), serious adverse events were reported in about 49% of patients receiving obinutuzumab and 43% for rituximab, indicating comparable safety profiles without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study. Townsend, W., Hiddemann, W., Buske, C., et al.[2023]

Obinutuzumab, a new anti-CD20 monoclonal antibody, has shown promising efficacy in treating follicular lymphoma (FL) and has been approved by the FDA for use in combination with bendamustine for patients who have relapsed after rituximab treatment.

Ongoing phase III trials, such as the GALLIUM trial, suggest that obinutuzumab may soon be established as a first-line treatment for FL, potentially replacing rituximab as the gold standard, although some safety concerns remain to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab in follicular lymphoma. Martinez-Calle, N., Figueroa-Mora, R., Villar-Fernandez, S., et al.[2017]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39776016/

The real-world efficacy and safety of frontline therapy ... With a median follow-up of 38.5 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 77.3% and 91.2%, respectively.

2. gazyva-hcp.com gazyva-hcp.com/follicular-lymphoma/efficacy/clinical-results.html

GALLIUM Trial Efficacy | First-Line Follicular Lymphoma Review GAZYVA® (obinutuzumab) progression-free survival (PFS) rates vs. rituximab product in first-line follicular lymphoma patients.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1614598

Obinutuzumab for the First-Line Treatment of Follicular ... Obinutuzumab-based immunochemotherapy and maintenance therapy resulted in longer progression-free survival than rituximab-based therapy.

4. ashpublications.org ashpublications.org/ashclinicalnews/news/2803/Obinutuzumab-Based-Induction-and-Maintenance

Obinutuzumab-Based Induction and Maintenance Prolongs ... An Independent Review Committee found similar results: The three-year PFS rate was 81.9 percent in the obinutuzumab arm and 77.9 percent in the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5551938/

Obinutuzumab for the treatment of indolent lymphoma - PMC The results were favorable with 86 to 100% ORR in the four different treatment arms and a CR rate of 45% over all treatment arms [55]. Based on these results ...

6. gazyva-hcp.com gazyva-hcp.com/rr-follicular-lymphoma/safety/important-safety-information.html

Indications and Important Safety Information Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients receiving CD20-directed ...

7. gazyva.com gazyva.com/

GAZYVA® (obinutuzumab) Treatment, Indications, Dosing ... Learn about GAZYVA® (obinutuzumab) for first-line, R/R follicular lymphoma & first-line CLL. See important safety including Boxed Warnings for more ...

8. ashpublications.org ashpublications.org/bloodadvances/article/8/4/878/498748/Safety-of-bendamustine-for-the-treatment-of

Safety of bendamustine for the treatment of indolent non ... 77 patients (24%) experienced 91 grade 3 to 5 infections, of which 44% were treatment-related SAEs, affecting 39 patients (12%).

9. gazyva.com gazyva.com/relapsed-refractory-fl/dosing-and-administration/treatment-schedule.html

R/R Follicular Lymphoma GAZYVA® (obinutuzumab) is a prescription medicine used with the chemotherapy drug, bendamustine, followed by GAZYVA alone for follicular lymphoma (FL) in adults ...