95 Participants Needed

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
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 2 JurisdictionsThis treatment is already approved in other countries

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.12345

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.12356

Research Team

PM

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.
See 26 more

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 OverviewThe 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
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (obinutuzumab, lenalidomide)Experimental Treatment8 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 Treatment8 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 Control12 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

Find a Clinic Near You

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.
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.
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.
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]

References

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. [2018]
Obinutuzumab: first global approval. [2021]
Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. [2021]
Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study. [2023]
Obinutuzumab in follicular lymphoma. [2017]
GA101 (a Novel Anti-CD20 Monoclonal Antibody)-Induced Lichenoid Eruption. [2022]