Obinutuzumab + Venetoclax + Lenalidomide for B-Cell Non-Hodgkin's Lymphoma

Not currently recruiting at 1 trial location

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Beth Christian

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: CNS involvement, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new combination of treatments to assess their effectiveness for individuals with B-cell Non-Hodgkin's lymphoma, particularly if the cancer has returned or resisted other treatments. The study combines three drugs: obinutuzumab, which may inhibit cancer cell growth; venetoclax, which might block certain enzymes to stop cancer cell growth; and lenalidomide, a chemotherapy drug that attacks cancer cells in multiple ways. The trial aims to determine the optimal doses and understand the side effects of these drugs when used together. Individuals with B-cell Non-Hodgkin's lymphoma who have tried at least one other treatment and still have measurable disease might be suitable candidates for the trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have taken venetoclax, lenalidomide, or certain other drugs recently. You also cannot use warfarin or certain other medications that interact with the trial drugs.

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

Earlier studies examined the safety of combining three drugs—obinutuzumab, venetoclax, and lenalidomide—to treat B-cell non-Hodgkin lymphoma. Research has shown that venetoclax is usually safe for patients, even when used alone for those with recurrent or difficult-to-treat lymphoma. The combination of obinutuzumab and lenalidomide also appeared safe, with manageable side effects.

These findings come from early-stage trials, which primarily assess safety and determine the appropriate dosage. Although data remains limited, current evidence suggests these treatments are generally safe for most patients. However, as this is an early-phase trial, further research is necessary to fully understand the safety and effectiveness of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of obinutuzumab, venetoclax, and lenalidomide for treating B-cell non-Hodgkin's lymphoma because it brings together three unique mechanisms of action. Obinutuzumab is a monoclonal antibody that targets the CD20 protein on B-cells, leading to their destruction. Venetoclax works by inhibiting the BCL-2 protein, which helps cancer cells survive, thereby promoting their death. Lenalidomide enhances the immune system's ability to attack cancer cells. This multi-targeted approach could potentially improve treatment effectiveness and overcome resistance seen in standard therapies like chemotherapy and other monoclonal antibodies.

What evidence suggests that this trial's treatments could be effective for B-cell non-Hodgkin lymphoma?

Research has shown that a combination of three drugs—obinutuzumab, venetoclax, and lenalidomide—may effectively treat B-cell non-Hodgkin lymphoma. Participants in this trial will receive this combination treatment. One study found that using these drugs together is not only feasible but also active against the cancer. Obinutuzumab helps stop cancer cells from growing. Venetoclax blocks certain proteins that cancer cells need to grow. Lenalidomide kills cancer cells and prevents them from multiplying and spreading. Together, these treatments aim to combat the cancer in different ways. ^{1 2 3 4 6}

Who Is on the Research Team?

Beth Christian, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with B-cell non-Hodgkin lymphoma that has come back or didn't respond to treatment. They must be in good physical condition, have not used certain drugs like venetoclax before, and have proper kidney function. Women who can get pregnant must follow strict pregnancy testing rules. People with severe allergies, recent major surgery, active infections, or other serious health issues cannot join.

Inclusion Criteria

This study has a separate group of participants called the "expansion cohort" who meet specific criteria for enrollment.

Absolute neutrophil count (ANC) >= 1000/mm^3

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria

You are allergic to both xanthine oxidase inhibitors and rasburicase.

Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction likely to interfere with the delivery, absorption, or metabolism of venetoclax or lenalidomide

Patients may take steroids for disease control up to 24 hours prior to study enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenalidomide orally on days 1-21, venetoclax orally on days 1-28, and obinutuzumab intravenously on days 1, 8, and 15 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for up to 12 courses.

Up to 12 months

Multiple visits per course

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

1 visit at 4 weeks, then every 3 months for 2 years, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Obinutuzumab
• Venetoclax

Trial Overview The study tests the combination of three drugs: Obinutuzumab (a monoclonal antibody), Venetoclax (blocks enzymes for cell growth), and Lenalidomide (chemotherapy). It aims to find the safest doses and see how well they work together against different types of B-cell non-Hodgkin lymphoma.

How Is the Trial Designed?

Group I: Treatment (lenalidomide, venetoclax, obinutuzumab) Experimental Treatment 3 Interventions

Patients receive lenalidomide PO on days 1-21 and venetoclax PO on days 1-28. Patients also receive obinutuzumab IV on days 1, 8, and 15 of course 1, and day 1 of courses 2-6. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Beth Christian

Lead Sponsor

Trials

3

Recruited

80+

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

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

The combination of venetoclax, ibrutinib, and obinutuzumab is well tolerated in patients with relapsed and untreated mantle cell lymphoma (MCL), with no dose-limiting toxicities reported and a maximum tolerated dose of 400 mg per day established for venetoclax.

High response rates were observed, with a complete response rate of 67% in relapsed patients and 86.6% in untreated patients, along with significant minimal residual disease clearance in 71.5% of relapsed and 100% of untreated patients after three cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. Le Gouill, S., Morschhauser, F., Chiron, D., et al.[2021]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

The study analyzed pharmacokinetics and exposure-response parameters of a 400 mg once-daily venetoclax regimen combined with obinutuzumab in 274 patients, confirming its suitability for first-line treatment of chronic lymphocytic leukemia (CLL).

No significant correlations were found between venetoclax exposure and progression-free survival or severe treatment-emergent adverse events, indicating that the treatment is both effective and safe at the studied dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Samineni, D., Gibiansky, L., Wang, B., et al.[2022]

In a phase 3 trial involving 432 patients with untreated chronic lymphocytic leukaemia, the combination of venetoclax plus obinutuzumab resulted in significantly longer progression-free survival compared to chlorambucil plus obinutuzumab, with a hazard ratio of 0.31, indicating a strong treatment advantage.

After a median follow-up of 39.6 months post-treatment, patients receiving venetoclax plus obinutuzumab had not yet reached median progression-free survival, while those on chlorambucil plus obinutuzumab had a median of 35.6 months, highlighting the long-term efficacy of the venetoclax regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Al-Sawaf, O., Zhang, C., Tandon, M., et al.[2020]

In a phase 2 trial involving 70 patients with chronic lymphocytic leukaemia, both 12 cycles of venetoclax consolidation and minimal residual disease-guided consolidation showed similar effectiveness, with around 50% of patients achieving undetectable minimal residual disease in bone marrow after treatment.

While consolidation treatment did not lead to treatment-related deaths, it was associated with a higher incidence of adverse events, particularly infections, indicating that while it may extend treatment duration, it does not significantly improve disease response or reduce relapse risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial. Kersting, S., Dubois, J., Nasserinejad, K., et al.[2022]

The combination of venetoclax and obinutuzumab was found to be safe and well-tolerated in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia, with no dose-limiting toxicities observed during the study.

The treatment resulted in a high overall response rate of 95% in relapsed/refractory patients and 100% in previously untreated patients, with significant rates of undetectable minimal residual disease, indicating effective disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Flinn, IW., Gribben, JG., Dyer, MJS., et al.[2021]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02992522?term=AREA%5BConditionSearch%5D(%22Lymphoma,%20Non-Hodgkin,%20Familial%22)%20AND%20AREA%5BInterventionSearch%5D(%22Obinutuzumab%22)&rank=8

Obinutuzumab, Venetoclax, and Lenalidomide in Treating ... This phase I study studies the side effects and best dose of venetoclax and lenalidomide when given together with obinutuzumab in treating patients with ...

2. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/4082/424313/Results-of-a-Phase-I-Study-of-Obinutuzumab

Results of a Phase I Study of Obinutuzumab, Venetoclax, and ... Conclusions: Combined treatment with obinutuzumab, venetoclax, and lenalidomide administered up to 12 cycles is feasible with activity in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9278307/

SAKK 35/15: a phase 1 trial of obinutuzumab in combination ... This phase 1 study evaluated safety, tolerability, and preliminary efficacy of obinutuzumab in combination with venetoclax in patients with ...

4. ashpublications.org ashpublications.org/blood/article/132/Supplement%201/4185/275455/Preliminary-Results-of-a-Phase-I-Study-of

Preliminary Results of a Phase I Study of Obinutuzumab ... Introduction: Combined obinutuzumab (O) and lenalidomide (L) has demonstrated safety and preliminary efficacy in follicular lymphoma1.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12234259/

Final analysis of a phase II trial from the LYSA group - PMC Atezolizumab, obinutuzumab and venetoclax for the treatment of patients with relapsed/refractory B non‐Hodgkin lymphoma: Final analysis of a phase II trial ...

6. blog-ecog-acrin.org blog-ecog-acrin.org/now-enrolling-ea4231-for-patients-with-relapsed-or-refractory-b-cell-lymphoma/

EA4231 for Patients with Aggressive B-cell Lymphoma Trial EA4231 is evaluating a new drug combination for patients with B-cell lymphoma that has relapsed after remission or no longer responds ...