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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety of giving the patient special cells from a donor called "Modified T-cells". The goal is to assess the toxicities of T-cells for patients with relapsed B cell leukemia or lymphoma after a blood SCT organ SCT or for patients who are at high risk for relapse of their B cell leukemia or lymphoma.

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.

What data supports the effectiveness of the treatment Modified T-cells for Leukemia and Lymphoma?

Research shows that genetically modified T cells, like those used in this treatment, have been successful in treating chronic lymphoid leukemia by significantly reducing tumors in patients. Additionally, similar therapies have shown promising results in preventing relapse in acute myeloid leukemia and treating other blood cancers. ^{1 2 3 4 5}

What safety data exists for genetically modified T cells used in leukemia and lymphoma treatment?

Genetically modified T cells, like CAR-T cells, have shown promise in treating blood cancers but come with safety concerns such as cytokine release syndrome (CRS), which is usually mild but can be severe, and neurotoxicity, which is infrequent. Strategies are being developed to manage these risks, and ongoing research is needed to fully understand their long-term safety. ^{6 7 8 9 10}

How is the treatment of genetically modified T cells for leukemia and lymphoma different from other treatments?

This treatment is unique because it involves genetically modifying T cells (a type of immune cell) to specifically target and attack cancer cells, which is different from traditional treatments like chemotherapy that affect both cancerous and healthy cells. By engineering T cells to recognize specific cancer antigens, this approach aims to enhance the body's natural immune response against tumors, potentially leading to more effective and targeted cancer treatment. ^{1 2 11 12 13}

Research Team

Kevin Curran

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

Pulmonary function: Oxygen saturation ≥ 90% on room air

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Chasing cancer with chimeric antigen receptor therapy. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy utilizing cancer antigen-specific T-cell receptors. [2017]

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

Gammaretroviral Production and T Cell Transduction to Genetically Retarget Primary T Cells Against Cancer. [2023]

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

TCR Gene Therapy Improves AML Prognosis. [2020]

5. Italy pubmed.ncbi.nlm.nih.gov

Genetic modification of human T lymphocytes for the treatment of hematologic malignancies. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. [2022]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Equipping CAR-modified T cells with a brake to prevent chronic adverse effects. [2019]

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

T-cell Immunotherapies and the Role of Nonclinical Assessment: The Balance between Efficacy and Pathology. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Challenges in T cell receptor gene therapy. [2023]

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

Genetic modification of T lymphocytes for adoptive immunotherapy. [2017]

12. England pubmed.ncbi.nlm.nih.gov

Targeting tumours with genetically enhanced T lymphocytes. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Genetic redirection of T cells for cancer therapy. [2010]