CAR-T Therapy for B-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Ariela Noy

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AIDS Malignancy Consortium

Must be taking: Antiretrovirals

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Pregnancy, CNS pathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a treatment called axicabtagene ciloleucel, a type of CAR-T therapy. This therapy uses modified T cells to target and kill cancer cells in individuals with HIV-associated aggressive B-cell non-Hodgkin lymphoma. The trial aims to determine the treatment's effectiveness and understand any side effects. It seeks participants with aggressive B-cell lymphoma that has either returned or not responded to previous treatments and who are living with HIV. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like corticosteroids, chemotherapy, and immunosuppressive therapies must be stopped within specific timeframes before certain procedures. It's best to discuss your current medications with the trial team to understand any necessary adjustments.

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

Research shows that axicabtagene ciloleucel, a type of CAR-T therapy, is usually well-tolerated by patients with certain B-cell lymphomas. In earlier studies, most patients experienced manageable side effects, such as fever and low blood cell counts. Serious side effects occurred less frequently, though some patients had severe reactions.

The FDA has already approved this treatment for other B-cell lymphomas, indicating well-documented safety. However, this trial is in an early stage and specifically examines safety for individuals with HIV-associated aggressive B-cell non-Hodgkin lymphoma. Participants should consult their healthcare provider about potential risks to understand how this treatment might affect them personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell lymphoma, which often include chemotherapy and radiation, axicabtagene ciloleucel is a CAR-T cell therapy that offers a novel approach by genetically modifying a patient's own T-cells to better recognize and attack cancer cells. This personalized treatment targets a specific protein, CD19, found on the surface of B-cell lymphoma cells, allowing for a more precise attack while potentially sparing healthy cells. Researchers are excited about axicabtagene ciloleucel because it can lead to longer-lasting remissions and offers hope for patients who haven't responded well to traditional therapies.

What evidence suggests that axicabtagene ciloleucel might be an effective treatment for B-cell lymphoma?

Research has shown that axicabtagene ciloleucel, a type of CAR-T therapy, holds promise for treating large B-cell lymphoma. In some studies, it helped patients live longer when their cancer returned or didn't respond to other treatments. Many patients who received this therapy experienced long-lasting remissions, with their cancer staying away for a while. The treatment has proven effective for different patient groups and has manageable side effects. This trial will evaluate axicabtagene ciloleucel, suggesting it could enhance the immune system's ability to find and destroy cancer cells in B-cell non-Hodgkin lymphoma. ^{1 2 4 5 6}

Who Is on the Research Team?

Ariela Noy

Principal Investigator

AIDS Malignancy Consortium

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HIV and aggressive B-cell non-Hodgkin lymphoma that's relapsed or resistant to treatment. They must have had at least two prior therapies including an anthracycline and rituximab, be PET-positive or have bone marrow involvement, and be in fairly good health (ECOG <=1).

Inclusion Criteria

I have received anthracycline and rituximab and my disease is resistant after 2 treatments.

Agreement to use adequate contraception for women of child-bearing potential and men

Documentation of HIV-1 infection by specific means

Exclusion Criteria

Pregnant or nursing women

I do not have any uncontrolled illnesses.

I have a history of heart conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients receive fludarabine and cyclophosphamide intravenously to prepare for CAR-T cell therapy

3 days

3 visits (in-person)

Treatment

Patients receive axicabtagene ciloleucel intravenously

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Weekly for 1 month, monthly for 5 months, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Axicabtagene Ciloleucel

Trial Overview The trial tests axicabtagene ciloleucel (CAR-T therapy), where patients' T cells are modified to target CD-19 on cancer cells. It aims to see how well these engineered T cells can treat the lymphoma.

How Is the Trial Designed?

Group I: Treatment (conditioning, axicabtagene ciloleucel) Experimental Treatment 3 Interventions

Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5, -4, and -3. Patients then receive axicabtagene ciloleucel IV over 30 minutes on day 0.

Axicabtagene Ciloleucel is already approved in United States, European Union for the following indications:

Approved in United States as Yescarta for:

• 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

Approved in European Union as Yescarta for:

• 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

Who Is Running the Clinical Trial?

AIDS Malignancy Consortium

Lead Sponsor

Trials

64

Recruited

9,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Kite, A Gilead Company

Industry Sponsor

Trials

45

Recruited

4,300+

Published Research Related to This Trial

Axicabtagene ciloleucel (axi-cel) demonstrated impressive efficacy in treating relapsed/refractory large B-cell lymphoma, with overall and complete response rates of 83% and 58%, respectively, in the pivotal ZUMA-1 trial with a median follow-up of 27.1 months.

While axi-cel shows promise, it is associated with significant toxicities, including cytokine release syndrome (CRS) in 7% to 14% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 31% to 55%, highlighting the need for careful patient management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. Halford, Z., Anderson, MK., Bennett, LL.[2021]

Yescarta (axicabtagene ciloleucel) is an engineered T-cell therapy that showed a 66% overall response rate and a 47% complete response rate in treating relapsed or refractory diffuse large B-cell lymphoma, based on a phase II study with a median follow-up of 15.1 months.

The therapy was associated with manageable adverse events, including cytokine release syndrome and neurological issues, making it a promising option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. Papadouli, I., Mueller-Berghaus, J., Beuneu, C., et al.[2022]

Axicabtagene ciloleucel and tisagenlecleucel are FDA-approved CAR T cell therapies specifically designed to target CD19 in patients with relapsed or refractory aggressive B cell non-Hodgkin lymphoma, marking a significant advancement in cellular immunotherapy.

Despite their transformative potential, there are ongoing concerns about the appropriate use and potential short- and long-term toxicities of these therapies, prompting expert consensus to guide clinicians in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Jain, T., Bar, M., Kansagra, AJ., et al.[2020]

Axicabtagene ciloleucel (axi-cel) is an FDA-approved CAR T-cell therapy specifically designed to target CD19, showing promise in treating relapsed or refractory aggressive non-Hodgkin's lymphomas, including diffuse large B-cell lymphoma.

While axi-cel has demonstrated significant efficacy in clinical trials (ZUMA-1 Phase I and II), it is associated with potential toxicities such as cytokine release syndrome and neurotoxicity, which pose challenges for safe administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma. Jain, MD., Bachmeier, CA., Phuoc, VH., et al.[2020]

In a Phase 2 study involving 17 Japanese patients with relapsed/refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 86.7%, indicating its efficacy as a treatment option.

While no dose-limiting toxicities were observed, all patients experienced grade ≥3 treatment-emergent adverse events, with the most common being neutropenia and cytokine release syndrome, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma. Kato, K., Makita, S., Goto, H., et al.[2022]

In a phase 3 trial involving 359 patients with early relapsed or refractory large B-cell lymphoma, treatment with axicabtagene ciloleucel (axi-cel) resulted in significantly longer overall survival compared to standard care, with a median follow-up of 47.2 months showing a hazard ratio for death of 0.73 (P = 0.03).

Axi-cel also demonstrated improved progression-free survival, with a median of 14.7 months compared to 3.7 months for standard care, indicating its efficacy as a second-line treatment option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. Westin, JR., Oluwole, OO., Kersten, MJ., et al.[2023]

In a study of 122 patients treated with axicabtagene ciloleucel (axi-cel) for relapsed aggressive B-cell non-Hodgkin lymphoma, the overall response rate was 70% and the complete response rate was 50%, indicating strong efficacy even in a post-commercial setting with relaxed eligibility criteria.

Patients eligible for the original ZUMA-1 trial had significantly better outcomes, including higher complete response rates (63% vs. 42%) and longer duration of response, progression-free survival, and overall survival, while the rates of severe side effects like cytokine release syndrome and neurotoxicity were consistent with those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Jacobson, CA., Hunter, BD., Redd, R., et al.[2022]

In a retrospective study of 275 patients with relapsed/refractory large B-cell lymphoma (LBCL) receiving axicabtagene ciloleucel (axi-cel), the overall response rate was 82% and the complete response rate was 64%, demonstrating strong efficacy similar to the original ZUMA-1 trial.

Safety profiles showed that 7% of patients experienced severe cytokine release syndrome and 31% had neurotoxicity, with a nonrelapse mortality rate of 4.4%, indicating manageable risks associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Nastoupil, LJ., Jain, MD., Feng, L., et al.[2022]

Axicabtagene ciloleucel (axi-cel) is an effective CAR T-cell therapy targeting CD19, showing high response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies, particularly after two or more lines of prior treatment.

Axi-cel is FDA-approved for adult patients with specific types of B-cell lymphomas, including diffuse large B-cell lymphoma, and is currently being studied for its efficacy in other B-cell malignancies in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. Sharma, P., King, GT., Shinde, SS., et al.[2018]

In a phase 2 trial involving 111 patients with refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 82%, with 54% achieving a complete response, indicating its efficacy as a treatment option.

The treatment was associated with significant adverse events, including neutropenia in 78% of patients and neurologic events in 28%, highlighting the need for careful monitoring of safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. Neelapu, SS., Locke, FL., Bartlett, NL., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301665

Survival with Axicabtagene Ciloleucel in Large B-Cell ... Axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8555382/

Outcomes of patients with large B-cell lymphoma ... Outcomes of patients with large B-cell lymphoma progressing after axicabtagene ciloleucel therapy ... Axi-cel induced durable remissions with a ZUMA-1 (Safety and ...

3. ashpublications.org ashpublications.org/blood/article/143/26/2722/515777/Real-world-and-clinical-trial-outcomes-in-large-B

Real-world and clinical trial outcomes in large B-cell ... Overall survival and most safety outcomes with axi-cel were consistent across race/ethnicity in relapsed/refractory large B-cell lymphoma.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03391466

NCT03391466 | Study of Effectiveness of Axicabtagene ... The goal of this clinical study is to assess whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36999993/

Safety and Efficacy of Axicabtagene Ciloleucel versus ... Axi-cel is an effective second-line curative-intent therapy with a manageable safety profile and improved PROs for patients ≥65 years with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02348216

NCT02348216 | Study Evaluating the Safety and Efficacy of ... A Comparison of Two-Year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients With Refractory Large B Cell Lymphoma. Blood (ASH Annual Meeting ...