Anakinra for Neurotoxicity Prevention in CAR-T Cell Therapy
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial tests a combination of two drugs, anakinra and axicabtagene ciloleucel (a CAR-T cell therapy), to determine if they can reduce side effects in individuals with difficult-to-treat or recurrent Non-Hodgkin lymphoma (NHL). The goal is to lower the chances of symptoms like nausea, headache, and confusion during treatment. Suitable candidates for this trial include those whose large B-cell lymphoma has returned or resisted treatment after at least two different therapies. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from potentially effective therapies.
Do I have to stop taking my current medications to join the trial?
The trial requires a break from certain medications before starting. You need to stop any systemic therapy at least 2 weeks or 5 half-lives before the trial, and steroids require a 7-day break. Check with the trial team about your specific medications.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that anakinra is generally safe for treating conditions like cytokine release syndrome (CRS) and immune-related nervous system issues. Even at higher doses, it is well-tolerated, with no major safety concerns. Anakinra effectively reduces severe nervous system side effects without affecting the treatment's success.
Real-world studies indicate that axicabtagene ciloleucel most commonly causes side effects involving the nervous and immune systems, such as confusion and mild memory problems. However, these side effects are manageable and do not outweigh the treatment's potential benefits.
Overall, previous studies have found both anakinra and axicabtagene ciloleucel to be safe, offering a promising option for reducing serious side effects in people with relapsed or difficult-to-treat Non-Hodgkin lymphoma.12345Why are researchers excited about this trial's treatments?
Unlike the standard treatments for CAR-T cell therapy-related neurotoxicity, which focus on managing symptoms after they occur, the combination of Anakinra and Axicabtagene Ciloleucel aims to prevent neurotoxicity from happening in the first place. Anakinra, an interleukin-1 receptor antagonist, works by blocking inflammatory pathways that contribute to neurotoxicity. Researchers are excited about this approach because it could lead to safer CAR-T cell therapies by reducing the risk of severe side effects, potentially improving patient outcomes and expanding the use of CAR-T therapy to more individuals.
What evidence suggests that this trial's treatments could be effective for preventing neurotoxicity in CAR-T cell therapy?
Research has shown that anakinra might help reduce side effects when combined with axicabtagene ciloleucel, a treatment for Non-Hodgkin lymphoma (NHL). In this trial, participants will receive both anakinra and axicabtagene ciloleucel. Studies have found that anakinra can ease symptoms of Cytokine Release Syndrome (CRS) and nerve-related issues. Previous findings suggest that this combination can delay or lessen these side effects. In some lab tests, anakinra prevented CRS and nerve problems. Although more information is needed, early results appear promising for those with relapsed or difficult-to-treat NHL.16789
Who Is on the Research Team?
Matt Frigault, MD
Principal Investigator
Massachusetts General Hospital
Are You a Good Fit for This Trial?
This trial is for adults over 18 with relapsed or resistant large B-cell lymphoma after two prior therapies. They must have at least one measurable lesion, stable recovery from previous treatments, good organ function, and no severe allergies to study drugs. Women of childbearing age need a negative pregnancy test and agree to use contraception.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Enrollment/Leukapheresis
Participants undergo leukapheresis to collect cells for CAR-T cell manufacturing
Bridging Therapy
Participants may receive bridging therapy if applicable
Lymphodepleting Chemotherapy
Participants receive lymphodepleting chemotherapy prior to CAR-T cell infusion
Investigational Product Treatment
Participants receive Anakinra and Axicabtagene Ciloleucel
Post Treatment Assessment
Participants are assessed for neurotoxicity and other adverse events
Long Term Follow-up
Participants are monitored for progression-free survival and overall survival
What Are the Treatments Tested in This Trial?
Interventions
- Anakinra
- Axicabtagene Ciloleucel
Trial Overview
The study tests if anakinra can reduce side effects like Cytokine Release Syndrome (CRS) and neurologic toxicities in patients receiving axicabtagene ciloleucel for Non-Hodgkin lymphoma. It's seeing if this combination is safer than the current treatment.
How Is the Trial Designed?
1
Treatment groups
Experimental Treatment
Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. * Screening * Enrollment/Leukapheresis period * Bridging therapy (if applicable) * Lymphodepleting chemotherapy period * Investigational Product (IP) treatment period * Anakinra * Axicabtagene Ciloleucel * Post treatment assessment period * Long term follow-up period
Axicabtagene Ciloleucel is already approved in United States, European Union for the following indications:
- Large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy
- Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
- Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy
- Relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy
- Relapsed or refractory follicular lymphoma after three or more lines of systemic therapy
Find a Clinic Near You
Who Is Running the Clinical Trial?
Marcela V. Maus, M.D.,Ph.D.
Lead Sponsor
Kite, A Gilead Company
Industry Sponsor
Citations
Clinical efficacy of anakinra to mitigate CAR T-cell therapy ...
Data regarding the clinical use of anakinra for the mitigation of axi-cel–associated toxicity have not been published. Patients with relapsed or ...
A Phase II Trial of Anakinra for the Prevention of CAR-T ...
Anakinra appears to provide benefit to the toxicity profile of axi-cel, presenting reduced and/or delayed CRS and NE and a decrease in post-infusion ...
3.
clinicaltrials.gov
clinicaltrials.gov/study/NCT04432506?term=Anakinra&cond=CAR-T&viewType=Table&rank=4Anakinra 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 ...
Anakinra for refractory CRS or ICANS after CAR T-cell therapy
In two preclinical murine models, anakinra could prevent CRS in immunodeficient Beige mice, and both CRS and ICANS in humanized SGM3 mice. Given ...
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 ...
Anakinra for Refractory Cytokine Release Syndrome or ...
Anakinra treatment for refractory CRS or ICANS was safe at doses up to 12 mg/kg/day iv. We observed an ORR of 77% after CAR-T therapy despite anakinra ...
7.
ashpublications.org
ashpublications.org/blood/article/142/Supplement%201/357/504089/A-Phase-II-Trial-of-Prophylactic-Anakinra-toA Phase II Trial of Prophylactic Anakinra to Prevent ...
Conclusion: Early use of prophylactic anakinra was safe, feasible and reduced the rate of severe ICANS without affecting efficacy in adult ...
Study Details | NCT04359784 | Anakinra for the Prevention ...
This phase II trial studies how well anakinra works in decreasing the occurrence of cytokine release syndrome (CRS) and damage to the nerves (neurotoxicity)
Anakinra for Refractory Cytokine Release Syndrome or ...
High-dose anakinra (up to 12 mg/kg/day) for refractory cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) was safe.
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