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

Trial Summary

What is the purpose of this trial?

This trial uses CAR T-cell therapy, which involves modifying a patient's immune cells to fight cancer. It targets patients with B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia who may not respond to standard treatments. The treatment works by collecting, modifying, and reinfusing the patient's own immune cells to attack cancer cells. CAR T-cell therapy has shown remarkable success in treating B-cell malignancies, including B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma.

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.

What data supports the effectiveness of the treatment CAR T-Cell Therapy for Lymphoma and Leukemia?

CAR T-cell therapies like Tisagenlecleucel (Kymriah) and Axicabtagene ciloleucel (Yescarta) have been approved for treating certain types of lymphoma and leukemia, showing effectiveness in patients with relapsed or refractory conditions. These treatments have transformed care for aggressive B-cell lymphomas and are specifically authorized for use in cases where other treatments have failed. ^{1 2 3 4 5}

Is CAR T-Cell Therapy safe for humans?

CAR T-Cell Therapy has been approved for certain types of lymphoma and leukemia, but it can have side effects. Some known side effects include cytopenias (low blood cell counts) and B-cell aplasia (loss of B cells), and there are strategies to manage these. Ongoing monitoring is important to manage potential long-term side effects. ^{3 4 5 6 7}

How is CAR T-Cell Therapy different from other treatments for lymphoma and leukemia?

CAR T-Cell Therapy is unique because it uses the patient's own immune cells, which are genetically modified to better recognize and attack cancer cells. This personalized approach, known as 'living drugs', is different from traditional treatments like chemotherapy, as it specifically targets cancer cells and can be administered in an outpatient setting. ^{2 4 5 7 8}

Research Team

John Lister, MD

Principal Investigator

AHN

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. France 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. France pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. [2021]

4. France 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]. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. [2020]

6. United States 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. [2022]

7. France 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)]. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. [2022]