Gene-Modified T Cells for Acute Lymphoblastic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: T cell suppressive therapy

Disqualifiers: CNS leukemia, Active malignancies, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for acute lymphoblastic leukemia (ALL) using specially modified T cells. These T cells, part of the immune system, are altered in a lab to recognize and attack leukemia cells. The main goal is to determine the safety of this approach and the correct dosage. Suitable candidates for this trial include those with a specific type of ALL, known as B-ALL, that has not responded to treatment or has recurred. Participants must also have their leukemia under control for a certain period before joining. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that specially modified T cells, like those used in this study, have been tested in several research projects. These T cells are altered in a lab to better target and attack cancer cells, specifically to combat leukemia. One study with 203 patients who had B-cell acute lymphoblastic leukemia (B-ALL) showed promising results with these modified T cells. However, reports indicate side effects, such as high rates of cancer recurrence. This suggests that while the treatment has potential, it also carries some risks.

The treatment under study is in an early phase, focusing on determining its safety and optimal dosage. Since it is still in early development, detailed safety information remains limited. However, its progression to human trials suggests that earlier studies found some initial safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about gene-modified T cells for treating acute lymphoblastic leukemia (ALL) because they offer a new way to target cancer. Unlike traditional treatments like chemotherapy, which attack all rapidly dividing cells, gene-modified T cells are engineered to specifically recognize and destroy cancer cells by targeting the CD19 protein on their surface. This precision reduces harm to healthy cells and may lead to fewer side effects. Additionally, this approach could be effective in patients who haven't responded well to other treatments, offering hope for those with relapsed or refractory disease.

What evidence suggests that gene-modified T cells might be an effective treatment for acute lymphoblastic leukemia?

Research shows that specially modified T cells have successfully treated acute lymphoblastic leukemia (ALL). In earlier studies, CD19-directed CAR T-cell therapy led to impressive remission rates. This therapy effectively targets cancer cells, even in patients with multiple relapses, and has been particularly beneficial for those with relapsed or difficult-to-treat blood cancers. The therapy works by adding a gene to T cells, enhancing their ability to find and destroy leukemia cells. Early results from other trials suggest this method holds promise for treating ALL. In this trial, participants with B Cell Acute Lymphoblastic Leukemia will receive gene-modified T cells, with doses adjusted based on the disease amount at infusion time. ^{2 3 4 6 7}

Who Is on the Research Team?

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

Citations

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Chimeric Antigen Receptor T-Cell Therapy Clinical Results ... Results from clinical trials across multiple institutions report remarkable remission rates with CD19-directed CAR-modified T-cell therapy.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000096

CAR T-cells for T-cell acute lymphoblastic leukemia CAR T-cells targeting CD19 antigen is a promising cancer immunotherapy obtaining excellent response rate in patients heavily pretreated for multiple relapses or ...

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CAR-T cell therapy for cancer: current challenges and ... This review offers an overview of the current development of CAR-T cell therapies for both hematologic and solid tumors, while examining the ...

4. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01737-8

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 ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2300709

Base-Edited CAR7 T Cells for Relapsed T-Cell Acute ... The interim results of this phase 1 study support further investigation of base-edited T cells for patients with relapsed leukemia.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11095278/

Comprehensive analysis of the efficacy and safety of CAR ... CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events.

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The present and future of CAR T-cell therapy for adult B-cell ALL Prior ALL treatments may compromise T-cell fitness, but for most CAR-T products, there are no absolute numeric lymphocyte cutoffs for leukapheresis. Early ...