Gene-Modified T Cells for Acute Lymphoblastic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

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

Compensation: Varies

Number of Visits: Unknown

93 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is an investigational approach that uses immune cells, called "T cells", to kill leukemia. These T cells are removed from blood, modified in a laboratory, and then put back in the body. T cells fight infections and can also kill cancer cells in some cases. However, right now T cells are unable to kill the cancer cells. For this reason we will put one gene into the T cells that allows them to recognize and kill the leukemia cells. This gene will be put in the T cells by a weakened virus. The gene will produce proteins in the T cells that help the T cells recognize the leukemia cells and possibly kill them. The doctors have found that T cells modified in this way can cure an ALL-like cancer in mice. The main goals of this study is to determine the safety and appropriate dose of these modified T cells in patients with ALL. This will be done in a "clinical trial." The dose of modified T-cells will depend on if you have disease present in your bone marrow or not. The patient will also receive chemotherapy before the T cells. We will use normally chemotherapy that is used in patients with leukemia. The chemotherapy is given to reduce leukemia and to allow the T cells to live longer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since chemotherapy is part of the treatment, it's best to discuss your current medications with the trial doctors to ensure there are no interactions.

What data supports the effectiveness of the treatment Gene-modified T cells for Acute Lymphoblastic Leukemia?

Research shows that gene-modified T cells, specifically CAR T-cells, have been highly effective in treating acute lymphoblastic leukemia (ALL), with complete remission rates over 70% in trials. This treatment has become a key option for patients with relapsed or hard-to-treat ALL, offering new hope where traditional methods have failed. ^{1 2 3 4 5}

Is gene-modified T cell therapy generally safe for humans?

Gene-modified T cell therapy, like CAR-T cell therapy, has shown promise in treating certain cancers, but it can cause serious side effects. Common side effects include cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), though these are often mild. Long-term safety is still being studied, and more research is needed to fully understand the risks. ^{1 4 6 7 8}

How does the treatment Gene-modified T cells differ from other treatments for acute lymphoblastic leukemia?

Gene-modified T cells, specifically CAR-T cell therapy, are unique because they involve genetically engineering a patient's own T cells to better recognize and attack leukemia cells. This approach is different from traditional treatments like chemotherapy and stem cell transplants, as it directly targets cancer cells with modified immune cells, offering a promising option for patients with relapsed or refractory acute lymphoblastic leukemia. ^{1 2 4 5 9}

Research Team

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with B-ALL leukemia that's resistant, relapsed, or in first complete remission can join. They need good heart and lung function, manageable blood chemistry levels, and a life expectancy over 3 months. Not allowed are those with recent heart attacks, severe heart failure, active GVHD from prior transplants, HIV/Hepatitis infections, active brain leukemia or other cancers needing treatment.

Inclusion Criteria

My B-ALL cancer has returned or is not responding to treatment.

My B-cell ALL is not responding to treatment, has returned, or is in the first complete remission.

MRD is defined as residual disease measured by specific methods

Exclusion Criteria

My leukemia has spread to my brain or spinal cord recently.

I had a stem cell transplant from a donor and am experiencing complications.

I have HIV, hepatitis B, or hepatitis C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive chemotherapy to reduce leukemia and allow T cells to live longer

2-3 weeks

T Cell Infusion

Participants receive genetically modified T cells to target leukemia cells

1 week

Follow-up

Participants are monitored for safety and effectiveness after T cell infusion

4 weeks

Treatment Details

Interventions

• Gene-modified T cells

Trial Overview The trial tests T cells genetically modified to target CD19 on leukemia cells after being reinfused into the patient. The study aims to find the safe dose of these T cells post chemotherapy which is given to reduce leukemia and help T cells last longer.

Participant Groups

Group I: Pts with B Cell Acute Lymphoblastic Leukemia Experimental Treatment 1 Intervention

This is a phase I study. Patients with CD19+ ALL (CR, relapsed, MRD, or refractory) are eligible for enrollment. B-ALL patients in first CR will be enrolled but only treated if they develop MRD or a frank relapse, while patients with MRD or with documented relapsed/refractory disease are eligible for immediate treatment. The T cell doses originally proposed in this study were based on doses administered safely in prior autologous T cell adoptive therapy trials but the dose has been modified based on the toxicities observed in patients with morphologic evidence of disease. Patients will be treated with different doses of T cells depending on the amount of disease at the time of T cell infusion. Patients in Cohort 1 (\<5% blasts in the BM) will continue to receive 10\^6 19-28z+ T cells/kg as previously. Patients in Cohort 2 (≥5% blasts in the BM) will receive the reduced dose of 1x106 19-28z+ T cells/kg).

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

CAR-T cell therapy targeting CD19 has been FDA-approved for treating relapsed and refractory acute lymphoblastic leukemia (ALL) in children and young adults, showing promising efficacy.

Recent trials with CD22-directed CAR-T cells indicate they can also effectively target leukemia, providing a potential alternative to CD19 therapy, although challenges like toxicity management and relapse rates remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. Pehlivan, KC., Duncan, BB., Lee, DW.[2019]

CAR T-cell therapy has significantly improved treatment options for acute lymphoblastic leukemia (ALL), achieving over 70% complete remission rates in clinical trials, and has been FDA approved for use in relapsed/refractory cases.

Despite its effectiveness, challenges such as relapse, resistance, and loss of CAR T-cell persistence pose barriers to long-term remission, highlighting the need for advancements in CAR T-cell engineering to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving CAR T-cells: The next generation. Marple, AH., Bonifant, CL., Shah, NN.[2021]

Adoptive transfer of antigen-specific T cells shows promise for treating viral infections in immunosuppressed patients, but achieving effective T-cell therapy for cancer is more challenging due to issues like T-cell tolerance and impaired survival in the body.

Genetic modification of T cells before transfer may help overcome obstacles such as tumor evasion tactics and improve the effectiveness of T-cell therapies for both cancer and infectious diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modification of T cells for immunotherapy. Berger, C., Berger, M., Feng, J., et al.[2019]

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]

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]

CAR T cell therapy, specifically targeting the CD19 antigen, has shown high response rates in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), indicating its potential as a new treatment option.

Despite its effectiveness, CAR T cell therapy is associated with severe toxicities like cytokine release syndrome and neurotoxicity, which pose challenges for its widespread use and highlight the need for ongoing improvements in the technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. Luskin, MR., DeAngelo, DJ.[2018]

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

CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer. [2018]

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

Improving CAR T-cells: The next generation. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Redirecting T cells with Chimeric Antigen Receptor (CAR) for the treatment of childhood acute lymphoblastic leukemia. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Genetic modification of T cells for immunotherapy. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. [2018]

9. England pubmed.ncbi.nlm.nih.gov

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