Genetically Modified T cells for Leukemia and Lymphoma

Overseen By Kevin Curran

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Glucocorticosteroids

Disqualifiers: HIV, Hepatitis B/C, Active malignancies, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

19 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using Modified T-cells, a type of immunotherapy, to determine their safety for people with certain blood cancers, such as B-cell leukemia or lymphoma. The trial focuses on patients whose cancer has returned after a transplant or who are at high risk of relapse. Participants may qualify if they have relapsed or are at high risk for relapse of B-cell leukemia or lymphoma, particularly after a stem cell or organ transplant. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systematic chemotherapy, you need to stop it at least 2 weeks before the infusion, unless it's intrathecal chemotherapy, hydroxyurea, oral maintenance chemotherapy, or steroid therapy at replacement doses, which have specific conditions.

Is there any evidence suggesting that Modified T-cells are likely to be safe for humans?

Studies have shown that CAR T-cell therapies, which use modified T-cells, can help patients with certain blood cancers like leukemia and lymphoma. These treatments modify the patient's own T-cells to better combat cancer cells. Some patients have experienced long periods of remission.

However, there are risks to consider. The FDA is investigating serious risks, including a rare type of T-cell cancer that can require hospitalization or be life-threatening. Although these risks are uncommon, they are important to consider when deciding to join a trial. Overall, researchers continue to study these therapies to understand their safety for everyone. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about genetically modified T cells for leukemia and lymphoma because they offer a targeted approach to fighting these cancers. Unlike traditional treatments like chemotherapy and radiation, which can affect healthy cells, genetically modified T cells are engineered to specifically recognize and attack cancer cells, minimizing damage to normal cells. This precision in targeting cancer cells allows for potentially more effective treatments with fewer side effects. Additionally, these T cells can be programmed to persist and provide ongoing surveillance against cancer recurrence, offering hope for long-term remission.

What evidence suggests that Modified T-cells might be an effective treatment for leukemia or lymphoma?

Research has shown that specially altered T-cells targeting the CD19 marker yield promising results in treating certain blood cancers. In this trial, participants will receive genetically modified T-cells as part of different expansion cohorts. Studies have found that these modified T-cells effectively combat difficult-to-treat B cell cancers, such as leukemia and lymphoma. In clinical trials, these treatments have led to significant improvements for patients with these diseases. For those with high-risk B cell cancers, these altered T-cells can locate and destroy cancer cells. While more research is needed to understand long-term effects, early results are hopeful for this type of treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Kevin Curran

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with B-cell leukemia or lymphoma who have had a stem cell transplant or are at high risk of relapse. They must have proper kidney, liver, heart, and lung function. It's not for those with active HIV/hepatitis infections, other cancers needing treatment, pregnant women, severe heart conditions, uncontrolled illnesses that could worsen side effects from the therapy.

Inclusion Criteria

My cancer has returned and tests show more than 5% cancer cells in my bone marrow or any cancer presence detected by specific tests.

My cancer returned after a stem cell or organ transplant.

My age does not limit my participation.

Exclusion Criteria

I have health issues that make it hard for me to handle side effects.

I am an adult with a heart condition.

I have an active HIV, hepatitis B, or hepatitis C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy prior to T-cell infusion

2-3 weeks

Treatment

Participants receive genetically modified T-cells to assess safety and toxicities

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after T-cell infusion

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Modified T-cells

Trial Overview The study tests the safety of Modified T-cells from donors targeting CD19 antigen in patients with relapsed B-cell malignancies post-transplant or at high risk of relapse. The focus is on assessing toxicities related to these genetically modified cells after chemotherapy conditioning.

How Is the Trial Designed?

Group I: Biological/Genetically Modified T cells Experimental Treatment 2 Interventions

Utilizing our initial trial experience, it was amended to include three (3) expansion cohorts. Cohort 1: patients with CD19+ relapse/refractory (R/R) B cell malignancies occurring after allogeneic/autologous HSCT or solid organ transplant (SOT) infusion occurring following conditioning chemotherapy. Cohort 2:patients with CD10+ high risk B cell malignancies eligible for autologous HSCT followed by 19-28z CRA EBV-CTLs (auto-HSCT preparative regimen serves as conditioning chemotherapy. Cohort 3: patients with CD19+ high risk B cell malignancies eligible for allogeneic HSCT followed by consolidative 19-28z CAR EBV-CTLs (allo-HSCT preparative regimen serves as conditioning chemotherapy) Each expansion cohort has a target accrual of 6 patients treated with fixed CAR EBV-CTL dose (3x106 EBV-CTLs/kg) which has been demonstrated to be the ideal manufacturing dose.

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

Genetic modification of T lymphocytes enhances their ability to recognize and attack tumor cells, which is crucial for improving cancer immunotherapy.

These modifications not only boost antitumor activity but also improve safety and allow for tracking of T cells using non-invasive imaging techniques, making them valuable for both research and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting tumours with genetically enhanced T lymphocytes. Sadelain, M., Rivière, I., Brentjens, R.[2021]

The article discusses a clinical trial for a new adoptive immunotherapy using gene-modified T cells that target the Wilms Tumor 1 (WT1) antigen, showing promise for treating refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

While this innovative approach has demonstrated clear and lasting clinical efficacy against tumors, it also poses risks of serious treatment-related adverse events, highlighting the need for careful management in developing powerful gene-modified T cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy utilizing cancer antigen-specific T-cell receptors. Tanimoto, K., Fujiwara, H.[2017]

In a small trial, T cells modified to target the Wilms tumor antigen 1 were effective in preventing relapse in patients with acute myeloid leukemia after they underwent an allogeneic stem-cell transplant.

This approach highlights the potential of engineered T cell therapies in enhancing post-transplant outcomes for leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCR Gene Therapy Improves AML Prognosis. [2020]

Recent advancements in T-lymphocyte based therapies, particularly through donor lymphocyte infusion and ex vivo expansion of antigen-specific cytotoxic T lymphocytes, have shown promising sustained antitumor effects in patients with virus-associated lymphomas, such as those related to Epstein-Barr virus.

The development of robust gene transfer methodologies to human T lymphocytes is rapidly evolving, providing new opportunities for enhancing the efficacy and specificity of T-cell based therapies in treating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modification of human T lymphocytes for the treatment of hematologic malignancies. Hoyos, V., Savoldo, B., Dotti, G.[2021]

Genetic modification of T cells to express receptors specific for tumor-associated antigens can redirect their function, enhancing their ability to target and eliminate tumor cells, which is crucial for treating common cancers.

Recent advances in gene design and cell production techniques have improved the clinical application of this adoptive immunotherapy, potentially leading to more effective treatments for patients with various types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic redirection of T cells for cancer therapy. Westwood, JA., Kershaw, MH.[2010]

CAR-based therapies for T-cell malignancies show promising clinical responses above 50%, but most studies have short follow-up periods, making long-term efficacy unclear.

Specific toxicities, such as cytokine release syndrome (CRS) and graft-versus-host disease (GvHD), are associated with CAR-T treatments, with CRS being more common in antiCD7 CAR-T cells, though generally mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies. Polgárová, K., Otáhal, P., Šálek, C., et al.[2022]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

Citations

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Novel cellular therapies for leukemia: CAR-modified T cells ... CAR-modified T cells targeted to the B cell–specific CD19 antigen have demonstrated promising results in multiple early clinical trials.

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Allogeneic off-the-shelf CAR T-cell therapy for relapsed or ... Postinfusion expansion and persistence were limited, and CAR EBV-VSTs demonstrated a unique T-cell phenotype compared with autologous 19-28z CAR ...

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Recent advances in universal chimeric antigen receptor T cell ... In recent years, CAR T cell therapy has shown remarkable efficacy in treating relapsed or refractory (r/r) hematological malignancies, such as B ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2473952925000801

Allogeneic off-the-shelf CAR T-cell therapy for relapsed or ... Our study demonstrates the feasibility and safety of an allogeneic “off-the-shelf” CAR EBV-VST product with favorable outcomes for patients with CD19+ R/R B- ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05418088

NCT05418088 | Genetically Engineered Cells (Anti-CD19 ... This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen ...

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

CAR-T cell therapy for cancer: current challenges and ... The primary challenge in developing CAR-T cell therapies for AML is the absence of an ideal target antigen that is both effective and safe, as ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6745952/

Chimeric Antigen Receptor-T Cell Therapy - PubMed Central CAR-T cell therapies, and in particular tisagenlecleucel, have demonstrated improved therapy outcomes for patients with relapsed/refractory B-ALL and DLBCL, and ...

8. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy Overall, the data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with ...

9. cancer.gov cancer.gov/about-cancer/treatment/research/car-t-cells

CAR T Cells: Engineering Immune Cells to Treat Cancer CAR T-cell therapy involves genetically engineering a patient's own T cells (red) to attack cancer cells (red and blue).

10. fda.gov fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous

FDA Investigating Serious Risk of T-cell Malignancy FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for ...