CAR T-Cell Therapy for Lymphoma and Leukemia

Overseen By Richard Wonder

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: John Lister

Must not be taking: Anticancer, Corticosteroids, Immunosuppressants, others

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 100

Duration: 30 days

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using CAR T-cells, a type of immune cell modified to better fight cancer, for individuals with certain blood cancers, specifically B-cell lymphoma and B-acute lymphoblastic leukemia. The goal is to determine if this treatment can be safely administered and if it benefits patients without other cure options. It suits those diagnosed with these cancers who have tried other treatments without success and still have measurable disease. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop certain medications, such as anti-cancer therapies, corticosteroids, and immunosuppressive drugs, at least 4 weeks before a procedure called leukapheresis. It's best to discuss your specific medications with the trial team to see if they need to be paused.

Is there any evidence suggesting that CAR T-Cell Therapy is likely to be safe for humans?

Research has shown that CAR T-cell therapy has been safely used to treat certain blood cancers. Approved CAR T-cell treatments have consistently been safe for conditions like B-Acute Lymphoblastic Leukemia. However, some risks require consideration. The FDA warns about the possibility of new cancer forming after treatment with certain CAR T-cell therapies. While the treatment is generally well-tolerated, there is a small chance of serious side effects. Most patients have managed the treatment well, but discussing any concerns with the clinical trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CAR T-Cell Therapy is unique because it uses a patient's own immune cells to fight cancer, specifically targeting lymphoma and leukemia. Unlike traditional treatments like chemotherapy or radiation, which attack cancer cells broadly, CAR T-Cell Therapy involves reprogramming a patient's T-cells to recognize and destroy cancer cells with precision. This personalized approach not only aims to be more effective but also reduces damage to healthy cells, potentially leading to fewer side effects. Researchers are excited about this treatment because it represents a significant shift towards more targeted cancer therapies, offering hope for long-term remission in patients who may not respond to conventional therapies.

What evidence suggests that CAR T-Cell Therapy might be an effective treatment for lymphoma and leukemia?

Research shows that CAR T-cell therapy has achieved impressive results in treating certain blood cancers like lymphoma and leukemia. This treatment uses a person's own immune cells to find and destroy cancer cells, and studies have shown it has strong effects against tumors. Data from past patients indicate that CAR T-cells can significantly shrink tumors and lead to long-lasting remission in many cases. Although challenges exist, the therapy has led to meaningful improvements in patient outcomes, making it a promising option for these conditions. Participants in this trial will receive CAR T-cell therapy, which involves CAR T-cell collection and infusion. ^{1 3 6 7 8}

Who Is on the Research Team?

John Lister, MD

Principal Investigator

AHN

Are You a Good Fit for This Trial?

Adults aged 18-79 with certain types of B-cell lymphoma or acute lymphoblastic leukemia that lack curative treatment options and have a life expectancy under two years. They must not be eligible for commercial CAR T-cell therapy, have measurable disease, and be able to understand the trial. Pregnant women, those unable to consent, or patients with active central nervous system cancer are excluded.

Inclusion Criteria

Your CD3 count in your blood is higher than 200/µL.

Subjects must have an expected survival > 12 weeks

I have B-cell cancer with no cure and am expected to live less than 2 years.

Exclusion Criteria

You have an active hepatitis B infection.

I have leukemia or lymphoma in my brain that hasn't been treated.

I haven't had cancer treatment within 4 weeks before my leukapheresis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Collection and Manufacturing

Cell collection by apheresis followed by CAR T-cell manufacturing

4-6 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CAR T-cell infusion

1 week

Treatment

CAR T-cell infusion on day 0 followed by monitoring for CRS, ICANS, and other toxicity

30 days

Daily visits in hospital from day 0 to day 14, then daily or thrice weekly to day 30

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

Monthly clinical examinations to day 100

Long-term Follow-up

Clinical follow-up every 3 months to day 730, then every 6 months to 5 years, and yearly up to 15 years

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Chimeric Antigen Receptor (CAR) T-Cell Product (Autologous)

Trial Overview The trial is testing locally manufactured CAR T-cells in treating various forms of B-cell lymphoma and acute lymphoblastic leukemia. It aims to show this method can safely create and administer these cells to help manage these cancers when other treatments aren't available.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

CAR -T-cell collection, infusion

Chimeric Antigen Receptor (CAR) T-Cell Product (Autologous) is already approved in United States, European Union for the following indications:

Approved in United States as CAR T-Cell Therapy for:

• B-Cell Lymphoma
• B-Acute Lymphoblastic Leukemia
• Multiple Myeloma
• Mantle Cell Lymphoma

Approved in European Union as CAR T-Cell Therapy for:

• B-Cell Lymphoma
• B-Acute Lymphoblastic Leukemia
• Multiple Myeloma
• Mantle Cell Lymphoma

Who Is Running the Clinical Trial?

John Lister

Lead Sponsor

Trials

1

Recruited

30+

Allegheny Health Network

Collaborator

Trials

7

Recruited

1,700+

Lentigen Technology, Inc.

Collaborator

Trials

1

Recruited

30+

AHN (Allegheny Health Network) Cancer Institute

Collaborator

Trials

1

Recruited

30+

Miltenyi Biotec, Inc.

Industry Sponsor

Trials

11

Recruited

280+

Published Research Related to This Trial

In a study of 72 adult patients with relapsed or refractory non-Hodgkin lymphoma treated with tisagenlecleucel, 94.4% received the therapy in an outpatient setting, demonstrating that this approach is both safe and feasible.

The overall response rate was 43%, with a complete response in 34.7% of patients, and serious adverse events like grade 3-4 cytokine release syndrome were not observed, indicating a manageable safety profile for outpatient CAR T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. Nasta, SD., Hughes, ME., Namoglu, EC., et al.[2022]

CAR T-cell therapies, such as tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), are effective treatments for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T cells that target the CD19 antigen.

These therapies are classified as 'living drugs' because they involve the genetic engineering of a patient's own T cells, highlighting the importance of proper collection and manufacturing processes for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. Carnoy, S., Beaumont, JL., Kanouni, T., et al.[2021]

CAR T cell therapy, specifically with tisagenlecleucel and axicabtagene ciloleucel, has been authorized in Europe for treating certain types of blood cancers, showing efficacy in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.

The recommendations provided focus on managing medium-term complications like cytopenias and B-cell aplasia, emphasizing the importance of supportive care for patients undergoing this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medium-term follow-up of patients treated with chimeric antigen receptor T cells (CAR T cells): Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Alsuliman, T., Drieu La Rochelle, L., Campidelli, A., et al.[2022]

CAR T-cell therapies have significantly changed treatment options for patients with relapsed or refractory aggressive B-cell lymphomas, with three products currently approved or nearing approval.

Selecting the right CAR T-cell product for a patient involves careful consideration of various factors, including the patient's age, health status, previous treatments, and the specific characteristics of each CAR T-cell product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection for chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell non-Hodgkin lymphomas. Johnson, PC., Abramson, JS.[2021]

CAR-T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have significantly improved outcomes for patients with relapsed or refractory aggressive B-cell lymphomas, with approvals based on pivotal trials demonstrating their efficacy after multiple prior treatments.

Despite their similar CAR technologies, differences in manufacturing and clinical trial designs exist between these therapies, highlighting the need for ongoing monitoring of patient responses and potential long-term side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Westin, JR., Kersten, MJ., Salles, G., et al.[2022]

A survey of 41 experienced clinicians revealed that many do not consider a history of malignancy or prior treatments as contraindications for CAR T-cell therapy, indicating a broader eligibility for patients than previously thought.

There is significant variability in follow-up care models after CAR T therapy, with most clinicians recommending frequent hospital visits in the initial month, highlighting the need for standardized guidelines in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. Hayden, PJ., Sirait, T., Koster, L., et al.[2021]

Chimeric antigen receptor (CAR) T-cell therapy, such as tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T-cells that target the CD19 antigen.

This collaborative work provides practical guidance for healthcare centers on how to select patients for these commercially available CAR T-cell therapies, ensuring appropriate use and maximizing treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. Beauvais, D., Bachy, E., Baruchel, A., et al.[2021]

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

Citations

1. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11305028/

Approved CAR-T therapies have reproducible efficacy and ... In pivotal clinical trials, CAR-T cells have demonstrated unprecedented anti-tumor efficacy leading to a shift in the treatment paradigm for ...

3. bloodcancerunited.org bloodcancerunited.org/blood-cancer-care/adults/types-blood-cancer-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy

Chimeric antigen receptor (CAR) T-cell therapy Autologous CAR T-cell immunotherapy uses a person's own immune cells (T cells) to identify and attack cancer cells.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1567576924008324

CAR-T cell therapy: Efficacy in management of cancers ... This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors.

5. chi.scholasticahq.com chi.scholasticahq.com/article/124277-overview-of-approved-car-t-products-and-utility-in-clinical-practice

Overview of approved CAR-T products and utility in clinical ... Below, we review the currently commercially available CAR T-cell products and their indications as of 2023.

6. fda.gov fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed

FDA Requires Boxed Warning for T cell Malignancies FDA Requires Boxed Warning for T cell Malignancies Following Treatment with BCMA-Directed or CD19-Directed Autologous Chimeric Antigen ...

7. mayoclinic.org mayoclinic.org/tests-procedures/car-t-cell-therapy/about/pac-20585020

CAR-T cell therapy CAR-T cell therapy is a cancer treatment that takes cells from the body and genetically changes them so they can fight cancer.

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.698607/full

Efficacy and Safety of CAR-T Cell Products Axicabtagene ... Efficacy and safety of CAR-T cell products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the treatment of hematologic ...