Obinutuzumab + Ibrutinib for Indolent Non-Hodgkin's Lymphomas

Overseen By Ubaldo Martinez-Outschoorn, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Must not be taking: Warfarin, CYP3A inhibitors

Disqualifiers: Prior malignancies, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining obinutuzumab and ibrutinib as a first treatment for individuals with indolent non-Hodgkin's lymphoma, a slow-growing blood cancer. Obinutuzumab (Gazyva) is a monoclonal antibody that may prevent cancer cells from growing and spreading, while ibrutinib (Imbruvica) blocks enzymes that aid cancer cell growth. The trial seeks participants with untreated indolent non-Hodgkin's lymphoma who require therapy and have measurable disease. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use warfarin, other vitamin K antagonists, or strong CYP3A inhibitors. You should also be off corticosteroids 2 weeks before starting the trial.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are using warfarin, other vitamin K antagonists, or require treatment with a strong CYP3A inhibitor. You should also be off corticosteroids for 2 weeks before joining the study.

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

Research shows that using obinutuzumab and ibrutinib together appears promising for treating a slow-growing type of non-Hodgkin's lymphoma. Several studies have examined the safety of these combined treatments.

For example, past research on obinutuzumab in various treatment settings indicates that most patients tolerate it well. Many patients have shown a good response, experiencing significant benefits. While some side effects might occur, they are manageable for most people.

Ibrutinib has also been extensively studied in combination with other treatments. It works by blocking certain proteins that help cancer cells grow. Although it can cause side effects, many patients continue treatment without major problems.

Overall, these studies provide a hopeful view of the safety of using obinutuzumab and ibrutinib together for this type of lymphoma. It's always important to discuss any concerns with a healthcare provider, who has the most current information and can help explain the benefits and risks based on individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of obinutuzumab and ibrutinib for treating indolent Non-Hodgkin's Lymphomas because it offers a potentially more effective approach compared to traditional therapies, which typically involve chemotherapy and rituximab. Obinutuzumab is a monoclonal antibody that specifically targets and destroys cancerous B-cells, while ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor that disrupts cancer cell signaling, leading to reduced growth and survival of the cancer cells. Together, these treatments work in tandem to more precisely attack the cancer from multiple angles, potentially offering improved outcomes and fewer side effects compared to standard chemotherapy regimens.

What evidence suggests that obinutuzumab and ibrutinib might be effective treatments for indolent non-Hodgkin's lymphoma?

This trial will evaluate the combination of obinutuzumab and ibrutinib for treating indolent non-Hodgkin's lymphoma. Research has shown that this combination works well for this slow-growing type of lymphoma. Studies have found that it helps shrink or eliminate tumors in 86 to 100% of patients, with 45% experiencing complete tumor disappearance. Patients generally tolerate this combination well, with few serious side effects. Overall, these findings suggest that this treatment could be a promising option for people with this type of lymphoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Ubaldo Martinez-Outschoorn, MD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for adults with untreated indolent non-Hodgkin's lymphoma, including various types of marginal zone and follicular lymphomas. Participants must have measurable disease, be able to swallow pills, and not have severe liver failure or other serious health conditions. Women of childbearing potential need a negative pregnancy test and agree to use effective contraception.

Inclusion Criteria

I have symptoms or conditions due to my lymphoma that require treatment.

I have a type of slow-growing non-Hodgkin's lymphoma known as follicular lymphoma.

My MZL cancer requires systemic therapy and has been confirmed with a biopsy.

Exclusion Criteria

I do not have active hepatitis B.

Patient is receiving other investigational drugs

I have hepatitis B but agree to treatment and monitoring while receiving obinutuzumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily and obinutuzumab intravenously on specified days, repeating every 28 days for up to 6 cycles

6 months

Multiple visits per cycle for IV administration

Maintenance

Participants with stable disease continue to receive obinutuzumab every 2 months for a total of 12 doses

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

7 years

Monthly for 1 year, every 3-6 months for 4 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Obinutuzumab

Trial Overview The study tests the combination of obinutuzumab (a monoclonal antibody) and ibrutinib (an enzyme blocker) as initial treatment for patients with certain types of slow-growing non-Hodgkin's lymphoma. The goal is to see if this drug combo can stop cancer cells from growing by interfering with their function.

How Is the Trial Designed?

Group I: Treatment (ibrutinib, obinutuzumab) Experimental Treatment 3 Interventions

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2 months after cycle 6, patients with stable disease will continue to receive obinutuzumab every 2 months for a total of 12 doses. After completion of study treatment, patients are followed up monthly for 1 year, every 3-6 months for 4 years, and then annually for up to 2 years.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

Sidney Kimmel Cancer Center at Thomas Jefferson University

Lead Sponsor

Trials

164

Recruited

10,900+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Pharmacyclics LLC.

Industry Sponsor

Trials

114

Recruited

13,800+

Dr. Maky Zanganeh

Pharmacyclics LLC.

Chief Executive Officer

Degree from Louis Pasteur University in Strasbourg, France; MBA from Schiller International University in France

Dr. Ellie Im

Pharmacyclics LLC.

Chief Medical Officer

MD from an unspecified institution

Published Research Related to This Trial

The Phase III GADOLIN trial showed that obinutuzumab combined with bendamustine significantly improves progression-free survival in patients with rituximab-refractory indolent non-Hodgkin lymphoma compared to bendamustine alone.

Obinutuzumab has received FDA approval for treating follicular lymphoma that has relapsed or is refractory to rituximab, highlighting its efficacy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab for the treatment of indolent lymphoma. Edelmann, J., Gribben, JG.[2018]

Obinutuzumab (Gazyva) is an effective treatment for chronic lymphocytic leukemia, targeting specific cancer cells to improve patient outcomes.

Ibrutinib (Imbruvica) is used for mantle-cell lymphoma and works by inhibiting a protein that helps cancer cells survive, while sofosbuvir (Sovaldi) effectively treats chronic hepatitis C by blocking the virus's ability to replicate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

In a phase II study involving 50 previously untreated patients with indolent mantle cell lymphoma (MCL), the combination of ibrutinib and rituximab resulted in an impressive 80% complete response rate after 12 treatment cycles.

The treatment also led to undetectable minimal residual disease (MRD) in 87% of patients, allowing 69% of evaluable patients to safely discontinue ibrutinib after 2 years, although caution is advised for those with TP53 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. Giné, E., de la Cruz, F., Jiménez Ubieto, A., et al.[2022]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

In a phase 3 study involving 396 patients with rituximab-refractory indolent non-Hodgkin lymphoma, the combination of obinutuzumab and bendamustine significantly improved progression-free survival compared to bendamustine alone, with a median not reached for the combination group versus 14.9 months for monotherapy.

The safety profile was manageable, with similar rates of grade 3-5 adverse events in both treatment groups, indicating that obinutuzumab plus bendamustine is a viable new treatment option for patients who have not responded to previous rituximab-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Sehn, LH., Chua, N., Mayer, J., et al.[2022]

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 treatment in patients with chronic lymphocytic leukemia and follicular lymphoma led to a significant decrease in natural killer (NK) cell levels in peripheral blood, dropping below the normal range.

Subcutaneous rituximab resulted in a less pronounced reduction of NK cells compared to intravenous rituximab, suggesting that the method of administration may influence NK cell levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army. García-Muñoz, R., Nájera, MJ., Feliu, J., et al.[2022]

In a phase 2 study involving 80 adults with untreated follicular lymphoma, the combination of ibrutinib and rituximab showed a high overall response rate of 85% in the first treatment arm and 75% in the second arm, indicating strong efficacy.

The treatment was generally well-tolerated, with common side effects including fatigue, diarrhea, and nausea, while serious adverse events were rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. Fowler, NH., Nastoupil, L., De Vos, S., 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]

Citations

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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 ...

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Clinical and Epidemiological Phase II, Single Arm, Open ... The chemotherapy free combination of Ibrutinib and Obinutuzumab is effective and well tolerated. The regimen was particularly effective in ...

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Study Details | NCT02689869 | Combination of PCI-32765 ... In patients remaining MRD positive at 30 months without clinical progression, single agent ibrutinib therapy is continued for another 12 months. An independent ...

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Advances in Lymphoma Research - NCI An early-phase NCI-supported study tested ibrutinib plus chemotherapy in people with primary central nervous system lymphoma, a very aggressive ...

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Imbruvica (Ibrutinib): First Drug Approved for the Treatment ... FDA expands approved use of Imbruvica for rare form of non-Hodgkin lymphoma: first drug approved to treat Waldenström's macroglobulinemia. Press release.

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Obinutuzumab in the treatment of B-cell malignancies Phase I/II data from 66 patients with relapsed indolent NHL who received the investigational combination of obinutuzumab plus lenalidomide (G-Len) demonstrated ...

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ROSEWOOD: A Phase II Randomized Study of ... In 33 patients with R/R FL treated with single-agent zanubrutinib, ORR was 36% (CR, 18%) and median progression-free survival (PFS) was 10.4 ...