Obinutuzumab-Based Therapy for Follicular Lymphoma

Recruiting at 500 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

95 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work better in treating patients with grade I-IIIa follicular lymphoma.

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.

What data supports the effectiveness of the drug Obinutuzumab-based therapy for follicular lymphoma?

Research shows that Obinutuzumab, when combined with bendamustine, significantly extends the time patients live without their disease getting worse compared to bendamustine alone. This combination also improved overall survival in patients with follicular lymphoma, making it a promising option for those who have not responded to or have relapsed after previous treatments. ^{1 2 3 4 5}

How is the drug Obinutuzumab unique in treating follicular lymphoma?

Obinutuzumab is a new type of anti-CD20 antibody that is engineered to enhance the immune system's ability to kill cancer cells, making it potentially more effective than the current standard treatment, rituximab. It is used in combination with bendamustine for patients who have not responded to or have relapsed after rituximab treatment, and it has shown promising results in prolonging survival in these patients. ^{1 2 3 5 6}

Research Team

Paul M Barr

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 (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]

References

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

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

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

Obinutuzumab: first global approval. [2021]

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

Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. [2021]

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

Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

Obinutuzumab in follicular lymphoma. [2017]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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