What side effects are associated with this type of intervention?

Common treatments for B-Cell Lymphoma, such as Bcl-2 inhibitors (e.g., venetoclax), BTK inhibitors (e.g., ibrutinib), and monoclonal antibodies (e.g., obinutuzumab), have distinct side effect profiles. Bcl-2 inhibitors can cause neutropenia, infections, and gastrointestinal issues. BTK inhibitors are associated with diarrhea, fatigue, musculoskeletal pain, and cardiovascular events like atrial fibrillation and hypertension. Monoclonal antibodies often lead to infusion-related reactions, neutropenia, and infections. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Several FDA-approved treatments for B-Cell Lymphoma include drugs with mechanisms of action similar to those being studied in the BGB-11417 trial. Zanubrutinib, a BTK inhibitor, has been approved for mantle cell lymphoma. Obinutuzumab, an anti-CD20 monoclonal antibody, is approved for use in combination with other drugs for follicular lymphoma and chronic lymphocytic leukemia. These treatments target specific pathways in B-cell malignancies, aiming to inhibit cancer cell growth and proliferation.

What other types of research exist?

Promising alternatives to BGB-11417 for B-Cell Lymphoma patients include venetoclax plus obinutuzumab, which has shown improved progression-free survival and acceptable tolerability. Another potential option could be KPT-SINE, given its preclinical efficacy in leukemia, though further studies are needed to confirm its applicability to B-Cell Lymphoma.

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Bcl-2 Inhibitor

BGB-11417 +/− Zanubrutinib for B-Cell Lymphoma

Phase 1

Recruiting

Research Sponsored by BeiGene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

- DLBCL, FL, MZL, SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable for this study

- CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry

Must not have

Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome

Prior therapy ≥ 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days after the last dose of study drug, an average of 18 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called BGB-11417 alone and with two other drugs to see if they are safe and how much can be given without serious side effects. It likely targets patients with certain cancers or blood disorders.

Who is the study for?

This trial is for adults with certain types of B-cell lymphoma who have relapsed or didn't respond to previous treatments. They must have measurable disease, be in fair health (ECOG 0-2), and their organs must function well. People with brain involvement by lymphoma, prior Bcl-2 inhibitor treatment failure, plasma cell neoplasm, prolymphocytic leukemia, or suspected Richter's syndrome can't join.

What is being tested?

The study tests the safety and ideal dosing of a new drug called BGB-11417 alone and combined with zanubrutinib and obinutuzumab. It aims to find the highest dose patients can take without serious side effects (MTD) and the recommended dose for future Phase 2 trials (RP2D).

What are the potential side effects?

Potential side effects include reactions related to infusion, changes in blood counts leading to increased infection risk or bleeding problems, liver issues indicated by abnormal blood tests, fatigue, nausea, diarrhea; specific risks will become clearer as more people participate.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a lymph node larger than 1.5 cm or an extranodal lesion larger than 1.0 cm.

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I have CLL with a lymph node larger than 1.5 cm or detectable cancer cells in my blood.

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My CLL/SLL diagnosis meets international standards.

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I can take care of myself and am up and about more than half of my waking hours.

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My follicular lymphoma has returned or didn't respond after at least one treatment.

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My marginal zone lymphoma has returned or didn't respond to treatment and needs more therapy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or am suspected to have a specific blood cancer type.

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I have been treated with a Bcl-2 inhibitor for at least 2 months or my condition worsened on it.

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My lymphoma/leukemia has spread to my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 days after the last dose of study drug, an average of 18 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 days after the last dose of study drug, an average of 18 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 days after the last dose of study drug, an average of 18 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: BGB-11417 Monotherapy Expansion Cohorts: Part 2Experimental Treatment1 Intervention

Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 at the RP2D dose to further define the safety profile

Group II: BGB-11417 Monotherapy Dose Finding: Part 1Experimental Treatment1 Intervention

Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral BGB-11417 until the maximum tolerated dose (MTD) (or maximum ascending dose (MAD)) and recommended phase 2 dose can be determined

Group III: BGB-11417 + Zanubrutinib Combination Therapy Dose Finding: Part 3Experimental Treatment2 Interventions

Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with zanubrutinib

Group IV: BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 6Experimental Treatment3 Interventions

Participants with treatment naïve CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with obinutuzumab without and with zanubrutinib

Group V: BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 4Experimental Treatment2 Interventions

Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with zanubrutinib

Group VI: : BGB-11417 + Zanubrutinib Combination Therapy Dose Escalation: Part 5Experimental Treatment2 Interventions

Participants with treatment naïve CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with obinutuzumab without and with zanubrutinib.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

obinutuzumab

2018

Completed Phase 3

~2630

Zanubrutinib

2017

Completed Phase 3

~2160

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for B-Cell Lymphoma include Bcl-2 inhibitors, BTK inhibitors, and monoclonal antibodies. Bcl-2 inhibitors, like venetoclax, induce apoptosis in cancer cells by inhibiting the Bcl-2 protein, which prevents cell death. BTK inhibitors, such as ibrutinib, block Bruton's tyrosine kinase, a key enzyme in the B-cell receptor signaling pathway, thereby inhibiting the growth and survival of malignant B-cells. Monoclonal antibodies, like rituximab, target specific antigens on the surface of B-cells, marking them for destruction by the immune system. These targeted therapies are significant for B-Cell Lymphoma patients as they offer more precise treatment options with potentially fewer side effects compared to conventional chemotherapy.

[Staging and Treatment Response Evaluation in Malignant Lymphomas - Czech Lymphoma Study Group Recommendations According to Criteria Revised in 2014 (Lugano Classification)].