Anakinra for CAR-T Cell Therapy Side Effects in Lymphoma

Not currently recruiting at 1 trial location

Overseen By Bianca Santomasso, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Infections, Hypersensitivity, Pregnancy, 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: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well anakinra (also known as Kineret) can alleviate the challenging side effects of CAR-T cell therapy, a treatment for certain types of lymphoma, a blood cancer. Researchers aim to determine if anakinra can prevent or reduce these side effects, making the therapy more tolerable for patients. The trial involves patients with specific forms of relapsed B-cell blood cancers undergoing CAR-T cell therapy. Participants should have experienced a recurrence of these blood cancers after treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that anakinra is generally safe, particularly for managing side effects from CAR-T cell therapy. In studies, participants tolerated anakinra well at doses up to 12 mg/kg per day administered through an IV. This dose exceeds what will be used in the trial, providing extra safety assurance.

Anakinra has been used in patients with severe symptoms after CAR-T therapy, such as cytokine release syndrome (CRS) and neurological side effects. These studies found that even at high doses, anakinra did not cause serious safety problems.

Based on current evidence, anakinra appears to be a safe option for managing side effects from CAR-T cell therapy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about using Anakinra for managing side effects of CAR-T cell therapy in lymphoma patients because it offers a novel approach to tackling the inflammation associated with this treatment. Unlike standard anti-inflammatory drugs, Anakinra specifically blocks the action of interleukin-1, a key player in the inflammatory response. This targeted action could mean better control of side effects like fevers and cytokine release syndrome, potentially improving patient comfort and outcomes during the critical early days post-therapy. Additionally, its administration through subcutaneous injections allows for easier and more flexible dosing compared to some existing treatments.

What evidence suggests that anakinra might be an effective treatment for CAR-T cell therapy side effects in lymphoma?

Studies have shown that anakinra can help manage severe side effects from CAR-T cell therapy, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). One study found that 77% of patients who received anakinra after CAR-T therapy experienced overall relief from these side effects. Another report noted that 4 out of 6 patients with severe ICANS improved with anakinra treatment. In this trial, participants will receive anakinra to evaluate its effectiveness in reducing the severity of these serious side effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed B-cell ALL, MCL, or NHL who are getting approved CD19-specific CAR T cell therapy. It's not for pregnant or breastfeeding women, those with uncontrolled infections, or anyone allergic to E. coli-derived proteins.

Inclusion Criteria

I am 18 or older with relapsed B-cell cancer and will receive approved CAR T cell therapy.

Exclusion Criteria

I am not pregnant or breastfeeding.

I do not have any uncontrolled fungal or bacterial infections.

I am not pregnant and cannot become pregnant due to surgery or being postmenopausal for 2+ years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anakinra to prevent or reverse severe side effects caused by CAR-T cell therapy. Cohort 1 receives anakinra 100mg s.c. every 12 hours starting on day 2 post CAR T cell infusion for 10 days. Cohort 2 receives anakinra 100mg s.c. daily starting on day 0 of T cell infusion for 7 days.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on severe neurotoxicities and other side effects.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anakinra

Trial Overview The study tests if anakinra can prevent or treat severe side effects in patients undergoing CAR-T cell therapy for certain blood cancers like lymphomas and leukemia.

How Is the Trial Designed?

Group I: Arm 1 (CART Cell Group) Experimental Treatment 1 Intervention

Cohort 1 Patients will receive anakinra 100mg s.c. every 12 hours starting on day 2 post CAR T cell infusion, or after 2 documented fevers of ≥38.5° C prior to day 2, whichever time point is earlier. Anakinra will be continued for 10 days. Cohort 2 Patients will receive anakinra 100mg s.c. daily on day 0 of T cell infusion, and continue anakinra daily for 7 days

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

CAR T cell therapy is effective in treating B cell malignancies like acute lymphoblastic leukemia and non-Hodgkin lymphomas, but it can also cause serious side effects, including multi-organ failure.

Early recognition and management of side effects such as cytokine release syndrome and neurotoxicity are crucial for healthcare staff to ensure patient safety during CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. Yáñez, L., Alarcón, A., Sánchez-Escamilla, M., et al.[2021]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

CAR T cell therapy, particularly with the approval of tisagenlecleucel, has shown remarkable efficacy in treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia, with six therapies approved as of April 2023 for B-cell malignancies and multiple myeloma.

However, the therapy is associated with significant adverse events like cytokine release syndrome, which are more severe with higher pretreatment tumor burdens; thus, initiating therapy early or using a debulking strategy may help mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. Mitra, A., Barua, A., Huang, L., et al.[2023]

CAR T cell therapy has shown significantly better response rates in patients with relapsed non-Hodgkin lymphoma compared to traditional salvage chemotherapy, indicating its efficacy in this challenging setting.

While CAR T therapy can lead to side effects like cytokine release syndrome and neurological events, most patients recover from these effects, suggesting a manageable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience of CAR T cell therapy in lymphomas. Oluwole, OO.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10330552/

Anakinra for refractory CRS or ICANS after CAR T-cell therapy Anakinra treatment for refractory CRS or ICANS was safe at doses up to 12mg/kg/day IV. We observed an ORR of 77% after CAR T-cell therapy ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723012332

Anakinra for Refractory Cytokine Release Syndrome or ... Anakinra treatment for refractory CRS or ICANS was safe at doses up to 12 mg/kg/day i.v. We observed an ORR of 77% after CAR-T therapy despite anakinra ...

3. ashpublications.org ashpublications.org/bloodadvances/article/4/13/3123/461283/Clinical-efficacy-of-anakinra-to-mitigate-CAR-T

Clinical efficacy of anakinra to mitigate CAR T-cell therapy ... In our series, 4 of 6 patients who received anakinra for the management of high-grade ICANS experienced clinical benefit. Although the onset of ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37031746/

Anakinra for Refractory Cytokine Release Syndrome or ... Anakinra treatment for refractory CRS or ICANS was safe at doses up to 12 mg/kg/day i.v. We observed an ORR of 77% after CAR-T therapy despite anakinra ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT372930

Role of anakinra in the management of icans after CAR T- ... Conclusions: In the reported cases, ICANS improved following administration of Anakinra, adding support to the idea that Anakinra may be beneficial in treatment ...

6. astctjournal.org astctjournal.org/article/S2666-6367(23)01233-2/pdf

Anakinra for Refractory Cytokine Release Syndrome or ... Anakinra treatment for refractory CRS or ICANS was safe at doses up to 12 mg/kg/day i.v. We observed an ORR of. 77% after CAR-T therapy despite ...

7. jeccr.biomedcentral.com jeccr.biomedcentral.com/articles/10.1186/s13046-021-02148-6

Mechanisms of cytokine release syndrome and ... CRS is the most common toxicity related to CAR T-cell therapy, with an incidence of 42–100%, and 0–46% of patients develop severe CRS after CAR ...