Glofitamab + Obinutuzumab for Mantle Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Anti-CD19 CAR T-cell

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: Active infection, Neurotoxicity, Cardiovascular disease, 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

Compensation: Varies

Number of Visits: 15

Duration: 36 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, glofitamab and obinutuzumab, for safety and effectiveness in people with mantle cell lymphoma. This cancer has either returned after treatment or hasn't responded to previous therapies, specifically after CAR T-cell therapy. Glofitamab helps the immune system find and attack cancer cells, while obinutuzumab may stop cancer cells from growing. People with mantle cell lymphoma that relapsed or didn't respond after CAR T-cell therapy might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain immunosuppressive medications or have not recovered from side effects of previous cancer treatments. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that glofitamab and obinutuzumab are likely to be safe for humans?

Research has shown that the combination of glofitamab and obinutuzumab has been studied in patients with mantle cell lymphoma (MCL), particularly those whose cancer has returned or resisted other treatments. Studies have found that glofitamab, in this context, generally has a manageable safety profile with appropriate care. While side effects can occur, they are often manageable with proper support.

In one study, patients who had undergone multiple previous treatments showed high rates of complete response (indicating the cancer responded well) with this combination therapy. Another study suggested that using glofitamab with obinutuzumab and an additional drug was safe and effective for individuals with relapsed or hard-to-treat MCL.

Although some side effects were noted, the overall safety data suggest these treatments are generally well-tolerated. This offers reassurance about the safety of trying glofitamab and obinutuzumab together for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments Glofitamab and Obinutuzumab for mantle cell lymphoma because they offer a novel approach that could enhance current therapies. Unlike traditional chemotherapy, which broadly attacks both healthy and cancerous cells, Glofitamab is a bispecific antibody designed to specifically target and engage the immune system to fight lymphoma cells. Obinutuzumab, on the other hand, is a type of monoclonal antibody that works by binding to the CD20 protein found on B-cells, leading to their destruction. This combination aims to provide a more targeted and potentially less toxic treatment option compared to conventional therapies, offering hope for improved outcomes.

What evidence suggests that glofitamab and obinutuzumab might be effective for mantle cell lymphoma?

Studies have shown that combining glofitamab and obinutuzumab holds promise for treating mantle cell lymphoma that has returned or resisted other treatments. Earlier research demonstrated that glofitamab alone helped 82% of patients by shrinking or eliminating their cancer, with 77% experiencing complete disappearance. Obinutuzumab targets and stops cancer cell growth, potentially enhancing treatment effectiveness. This trial will evaluate the combination of glofitamab and obinutuzumab, aiming to harness the immune system to more effectively attack and destroy cancer cells. Early results suggest this approach could benefit patients who haven't succeeded with other treatments. ^{1 5 6 7 8}

Who Is on the Research Team?

Cole H Sterling

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with mantle cell lymphoma that has returned or didn't respond after CAR-T cell therapy and BTK inhibitor treatment. Participants need a certain level of neutrophils, measurable cancer on CT scans, decent physical health (ECOG ≤ 2), adequate platelets, normal bilirubin levels (or slightly higher if they have Gilbert syndrome), and acceptable liver and kidney function.

Inclusion Criteria

My white blood cell count is healthy.

My platelet count is at least 50,000 per microliter.

My bilirubin levels are within the normal range, or slightly higher if I have Gilbert syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive obinutuzumab IV on day 1 or on days 1 and 2 of cycle 1 and glofitamab IV over 8 hours on days 8 and 15 of cycle 1 then over 2-8 hours on day 1 of cycles 2-12. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

36 weeks

12 cycles, each 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Glofitamab
• Obinutuzumab

Trial Overview The trial tests glofitamab combined with obinutuzumab in patients whose mantle cell lymphoma relapsed or was refractory post-CAR-T therapy. Glofitamab is a bispecific antibody targeting T cells and lymphoma cells; obinutuzumab targets cancer growth. The study evaluates safety, tolerability, and effectiveness.

How Is the Trial Designed?

Group I: Treatment (obinutuzumab, glofitamab) Experimental Treatment 5 Interventions

Patients receive obinutuzumab IV on day 1 or on days 1 and 2 of cycle 1 and glofitamab IV over 8 hours on days 8 and 15 of cycle 1 then over 2-8 hours on day 1 of cycles 2-12. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET/CT throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02470

Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma After a median follow-up of 19.6 (range, 0-39) months, 60 patients were efficacy-evaluable (one patient received no study treatment).

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1631/531703/Glofitamab-Induces-High-Response-Rates-and-Durable

Glofitamab Induces High Response Rates and Durable ... Glofitamab Induces High Response Rates and Durable Remissions in Patients (Pts) with Heavily Pretreated Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39365960/

Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03075696

NCT03075696 | A Dose Escalation Study of Glofitamab ... This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a ...

5. onclive.com onclive.com/view/glofitamab-produces-durable-remissions-in-r-r-mantle-cell-lymphoma

Glofitamab Produces Durable Remissions in R/R Mantle ... Glofitamab-gxbm monotherapy achieved an 82% overall response rate and 77% complete response rate in relapsed/refractory mantle cell lymphoma ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06054776

NCT06054776 | Acalabrutinib, Obinutuzumab, and ... Giving acalabrutinib, obinutuzumab, and glofitamab together may be a safe and effective treatment for patients with relapsed or refractory mantle cell lymphoma.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761309Orig1s000MultidisciplineR.pdf

761309Orig1s000 - accessdata.fda.gov The total safety data available allow for a comprehensive assessment of the safety profile of glofitamab ... cell lymphoma, MCL=mantle cell lymphoma, IIV= ...

8. ctsearchsupport.org ctsearchsupport.org/clinical-trials/a-study-of-glofitamab-and-lenalidomide-in-people-with-mantle-cell-lymphoma

A drug, glofitamab, in combination with lenalidomide and ... If the combination of glofitamab, lenalidomide and obinutuzumab is safe and works well to treat MCL that has relapsed or is refractory. You may ...