Anakinra for Large B-Cell Lymphoma

Not currently recruiting at 1 trial location

Overseen By Caspian Oliai

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Primary CNS lymphoma, Burkitt's lymphoma, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether anakinra can prevent encephalopathy, a serious brain condition, after CAR T-cell therapy in individuals with large B-cell lymphoma that hasn't responded to treatment. Anakinra calms the immune system and might prevent this complication. The trial targets those with this lymphoma type who have tried at least two unsuccessful treatments and qualify for a specific CAR T-cell therapy. Participants should have experienced lymphoma recurrence or persistence after a stem cell transplant or other recent treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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, certain treatments like alemtuzumab, clofarabine, cladribine, and immune checkpoint inhibitors must have been stopped for a specific period before joining the trial.

Is there any evidence suggesting that anakinra is likely to be safe for humans?

Research shows that anakinra, tested to prevent certain side effects from CAR T-cell therapy in large B-cell lymphoma, is generally well-tolerated. Previous studies demonstrated that anakinra, already approved for other uses, did not require initial safety testing due to its established safety profile. However, evidence suggests that while anakinra helps manage side effects, it might not completely prevent all of them. Thus, it may not stop every side effect, but it remains safe enough for further testing in this trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for large B-cell lymphoma?

Researchers are excited about anakinra for large B-cell lymphoma because it offers a new way to manage immune-related side effects from CAR T-cell therapy. Unlike standard treatments that primarily focus on directly targeting the cancer cells, anakinra works by modulating the immune response, specifically targeting IL-1 to reduce inflammation. This approach can potentially manage severe side effects like ICANS and CRS more effectively, allowing patients to better tolerate the powerful CAR T-cell therapy. By addressing these side effects, anakinra could improve the overall safety and effectiveness of current lymphoma treatments.

What evidence suggests that anakinra might be an effective treatment for large B-cell lymphoma?

In this trial, participants will receive a combination of treatments, including anakinra and CAR T-cell therapy, to manage large B-cell lymphoma. Research has shown that anakinra can reduce severe side effects from CAR T-cell therapy. Studies have found that anakinra is particularly effective in managing nerve damage unresponsive to steroids. In one instance, anakinra helped a patient with severe symptoms that other treatments couldn't control. Further research suggests that anakinra, when combined with axicabtagene ciloleucel, may help control lymphoma unresponsive to other treatments. However, some studies indicate that using anakinra once a day might not prevent all severe side effects. Overall, anakinra shows promise in managing challenging cases of this lymphoma. ^{1 2 4 5 6}

Who Is on the Research Team?

John Timmerman, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with large B-cell lymphoma that has returned or hasn't responded to two prior treatments. They must have certain blood test levels within normal ranges, be able to make medical decisions, and not be pregnant or nursing. People with primary CNS lymphoma, certain other cancers, recent chemotherapy or stem cell transplants, untreated infections, or uncontrolled autoimmune diseases cannot join.

Inclusion Criteria

People with HIV who have very low levels of the virus in their blood can participate.

I am considered capable of making my own medical decisions.

My large B-cell lymphoma has spread to my brain but did not start there.

Exclusion Criteria

I have an autoimmune disease that has caused organ damage or needed strong medication in the last 6 months.

I finished my last chemotherapy less than a week ago before starting CAR T-cell therapy.

My last scan was over 6 weeks ago before my CAR T-cell treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Therapy

Participants receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3

1 week

CAR T-cell Infusion

Participants receive axicabtagene ciloleucel CAR T-cell infusion

1 day

Anakinra Treatment

Participants with clinical evidence of ICANS or CRS receive anakinra subcutaneously every 6-12 hours for 12-36 doses over 9 days

9 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months

Follow-up visits at 30, 90, and 100 days, then at 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Anakinra

Trial Overview The study tests if anakinra can prevent severe brain-related side effects after CAR T-cell therapy in patients with large B-cell lymphoma. Anakinra is given alongside FDA-approved axicabtagene ciloleucel and standard drugs fludarabine and cyclophosphamide used before CAR T-cell treatment.

How Is the Trial Designed?

Group I: Prevention (anakinra, CAR T-cell therapy) Experimental Treatment 5 Interventions

Patients receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3, then receive axicabtagene ciloleucel CAR T-cell infusion. Patients with clinical evidence of ICANS of any grade, or CRS \>= grade 3 receive anakinra SC every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7362369/

Clinical efficacy of anakinra to mitigate CAR T-cell therapy ... Clinical efficacy of anakinra to mitigate CAR T-cell therapy–associated toxicity in large B-cell lymphoma

2. jhoponline.com jhoponline.com/issue-archive/2023-issues/february-2023-vol-13-no-1/anakinra-used-in-a-patient-with-diffuse-large-b-cell-lymphoma-and-steroid-refractory-immune-effector-cell-associated-neurotoxicity-syndrome-case-report

Anakinra Used in a Patient with Diffuse Large B-Cell ... This case provides insight into the early use of anakinra for the treatment of steroid-refractory ICANS and the management of antiepileptic therapies.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11462637/

Anti-CD19 CAR T cell therapy and prophylactic anakinra in ... We initiated a phase 2 clinical trial of anakinra in patients with relapsed/refractory large B-cell lymphoma and mantle cell lymphoma treated with commercial ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04432506?term=AREA%5BInterventionSearch%5D(%22Cyclophosphamide%22)&rank=8

Anakinra for the Reduction of CAR-T Toxicity in Patients ... Giving anakinra in combination with axicabtagene ciloleucel may help control relapsed or refractory large B-cell lymphoma. Detailed Description. PRIMARY ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2473952925000928

Single-cell dynamics of breakthrough toxicities after ... Our study, in line with others, demonstrates that once-daily prophylactic anakinra is insufficient to prevent the development of toxicities that would require ...

6. ashpublications.org ashpublications.org/bloodadvances/article/9/9/2122/535555/Single-cell-dynamics-of-breakthrough-toxicities

Single-cell dynamics of breakthrough toxicities after anakinra ... Because anakinra already has a safety label and did not require phase 1 testing, we performed a phase 2 clinical trial studying prophylactic ...