CAR T Cell Therapy for Acute Lymphoblastic Leukemia

Overseen By Aimee Talleur, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Primary immunodeficiency, HIV, Severe infection, 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

Compensation: Varies

Number of Visits: 3

Duration: 1 week

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment using modified immune cells, called CD19-CAR T cells (a type of immunotherapy), to target and kill leukemia cells. Researchers aim to assess how the body processes the chemotherapy drugs fludarabine and cyclophosphamide, the duration of CAR T cell activity, and the treatment's effectiveness for individuals whose leukemia has returned or hasn't responded to other treatments. The trial also examines potential side effects of this therapy. Individuals with leukemia that has returned or didn't respond to treatment, particularly those ineligible for a bone marrow transplant, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that CD19-CAR T cell therapy is generally safe. In studies, many side effects were mild, such as fatigue or fever, and can usually be managed. Serious side effects occur less frequently and often respond to medical treatment.

For example, one study found that most side effects were mild to moderate, indicating they weren't severe. Another study demonstrated that the therapy helped many patients achieve remission. This suggests that the benefits might outweigh the risks for some individuals.

Prospective trial participants should know that this treatment is still under investigation to confirm its safety and effectiveness. Consulting a doctor is essential to determine if it is a suitable option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for acute lymphoblastic leukemia, which typically involve chemotherapy and stem cell transplants, CD19-CAR T cell therapy offers a novel approach. This treatment uses a patient's own immune cells, which are modified to better recognize and attack cancer cells. Researchers are excited because this targeted method could lead to more effective and lasting responses, potentially reducing the need for more toxic treatments. Additionally, CAR T therapy has shown promise in producing rapid and significant improvements, making it a game-changer for patients who have not responded to traditional therapies.

What evidence suggests that CD19-CAR T cell therapy might be an effective treatment for leukemia?

Research has shown that CD19-specific CAR T cell therapy, which participants in this trial will receive, effectively treats acute lymphoblastic leukemia, particularly in patients whose cancer has returned or is unresponsive to other treatments. Studies have found that 70 to 90% of both children and adults achieve complete remission, meaning no signs of cancer, after this treatment. Many patients experience long-lasting results, with some studies noting that remission can last 12 months or more for a significant number of patients. Survival rates are also encouraging, with some therapies showing that up to 85% of patients remain alive 12 months after treatment. These findings suggest that CD19-CAR T cell therapy could offer a strong chance of remission for leukemia patients. ^{1 3 4 5 6}

Who Is on the Research Team?

Aimee Talleur, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young patients with CD19-positive leukemia, such as Acute Lymphoblastic Leukemia or Lymphoma, who have not responded to previous treatments or whose cancer has returned. Specific eligibility criteria are not provided but typically include age range and health status requirements.

Inclusion Criteria

My leukemia returned after a stem cell transplant.

My leukemia has returned, I can't have a stem cell transplant, and my cancer is CD19 positive.

I am 21 years old or younger.

Exclusion Criteria

Known primary immunodeficiency

I have a history of HIV infection.

I do not have a severe infection right now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Collection and Manufacturing

Patient blood cells are collected via apheresis and modified to recognize and kill cancer cells

2-3 weeks

Treatment

Participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by an infusion of CD19-CAR T cells

1 week

3 visits (in-person) for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CD19-CAR T cell

Trial Overview The study tests lymphodepleting chemotherapy followed by CAR T cell therapy in children and young adults. It aims to find the right dose of fludarabine before CAR T cell infusion, understand how the body processes drugs used, track how long CAR T cells stay active in the body, and assess effectiveness and side effects.

How Is the Trial Designed?

Group I: CAR19PK Therapy Experimental Treatment 4 Interventions

This study contains two phases. Collection and Manufacturing Phase: Patient blood cells will be collected, and possibly frozen, via a process called apheresis. These cells will then be changed to improve their ability to recognize and kill cancer cells. Treatment Phase: Patients that meet eligibility for treatment will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by an infusion of CD19-CAR T cells that were made in the Collection and Manufacturing Phase.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

CD19-specific CAR T-cell therapy shows high initial remission rates (over 80%) in pediatric patients with relapsed or refractory B-ALL, but only 40% to 50% achieve durable remission.

The review discusses the potential benefits of consolidative hematopoietic cell transplantation for patients who achieve a complete response after CAR T-cell therapy, as well as strategies to enhance the effectiveness and longevity of CAR T cells in preventing relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing relapse after CD19 CAR T-cell therapy for pediatric ALL: the role of transplant and enhanced CAR T cells. Talleur, AC., Naik, S., Gottschalk, S.[2023]

The study found that high levels of leukemia blast contamination in the starting material did not negatively impact the manufacturing of CAR T-cells or their ability to expand, suggesting that CAR T-cell therapy can be safely produced even from contaminated samples.

Using a specific CAR design with a short linker (CAR.CD19 SL) enhances the ability of CAR T-cells to target and kill CD19+ leukemia cells, providing a potential safety advantage in preventing leukemic relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. Quintarelli, C., Guercio, M., Manni, S., 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]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

CD19CAR-T cell therapy is effective in treating relapsed and refractory B-lineage acute lymphoblastic leukemia, with four out of five patients achieving complete remission and minimal residual disease negativity.

The therapy can be safely administered with real-time monitoring of a 6-cytokine pattern, allowing for effective management of side effects like cytokine release syndrome and neurotoxicity using tocilizumab and steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy can be administered safely under the real-time monitoring of Th1/Th2 cytokine pattern using the cytometric bead array technology for relapsed and refractory acute lymphoblastic leukemia in children. Shen, D., Song, H., Xu, X., et al.[2021]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

In a study of 15 patients with B cell acute lymphoblastic leukemia (B-ALL) who experienced extramedullary relapse, CD19 CAR-T cell therapy resulted in a high overall response rate of 93.3%, with 73.3% achieving complete response and a median duration of response of 6 months.

The therapy was associated with manageable adverse effects, including cytokine release syndrome in 86.7% of patients, but these were well controlled, indicating that CD19 CAR-T cell therapy is both effective and relatively safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19 CAR-T cell therapy for patients with B cell acute lymphoblastic leukemia involving extramedullary relapse. Huang, L., Zhang, M., Wei, G., et al.[2022]

In a phase 1 trial of 53 adults with relapsed B-cell acute lymphoblastic leukemia, 83% achieved complete remission after receiving CD19-specific CAR T cells, indicating high initial efficacy.

Patients with a low disease burden before treatment experienced significantly longer overall survival (20.1 months) and fewer severe side effects, such as cytokine release syndrome, compared to those with a higher disease burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. Park, JH., Rivière, I., Gonen, M., et al.[2023]

In a phase 1 trial involving 45 children and young adults with relapsed or refractory B-lineage acute lymphoblastic leukemia, a defined CD19 CAR T cell product achieved an impressive 89% rate of minimal residual disease-negative (MRD-) remission, indicating strong efficacy.

The trial demonstrated a favorable safety profile, with no deaths or severe toxicities like cerebral edema, although 23% of patients experienced reversible severe cytokine release syndrome or neurotoxicity, suggesting manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Gardner, RA., Finney, O., Annesley, C., et al.[2022]

CAR T cell therapy, particularly targeting CD19, has shown promising results in treating pediatric patients with relapsed and refractory B cell acute lymphoblastic leukemia (ALL), offering a new hope for those with high-risk disease.

The review highlights the need for exploring additional therapeutic targets for other high-risk leukemia types, such as T cell ALL, acute myeloid leukemia (AML), and infant ALL, to improve treatment outcomes in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond CD19: Opportunities for Future Development of Targeted Immunotherapy in Pediatric Relapsed-Refractory Acute Leukemia. Shalabi, H., Angiolillo, A., Fry, TJ.[2022]

CAR-T cell therapy, particularly with anti-CD19 CAR-T cells like Tisagenlecleucel (Kymriah®), has significantly improved treatment outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL), achieving high rates of remission.

While CAR-T therapy can lead to serious adverse events such as cytokine release syndrome and neurotoxicity, these are managed effectively in real-world settings, resulting in fewer severe complications compared to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of CAR-T cell therapy for pediatric hematologic malignancies. Hiramatsu, H.[2023]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/11/2763/536292/Real-world-outcomes-for-young-adult-patients

Real-world outcomes for young adult patients receiving CD19 ... Key PointsReal-world efficacy among YAs receiving CD19 CAR T was comparable irrespective of CAR T construct.CRS and ICANS were observed more ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40127395/

Real-world outcomes for young adult patients receiving CD19 ... Durability of remission over 12 months was 61% for brexu-cel vs 41% for tisa-cel; 12-month overall survival (OS) for brexu-cel was 84% vs 68% ...

3. nature.com nature.com/articles/s41409-025-02629-8

Clinical outcomes of a new local CD19 CAR-T cell therapy ... At median follow-ups of 12 and 36 months, durable responses were achieved in 57.1% of B-NHL patients treated with PP CAR-T, comparable to 60.4% ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709919

Long-Term Follow-up of CD19 CAR Therapy in Acute ... Multiple clinical trials of CD19-specific CAR T cells have shown complete remission rates of 70 to 90% among children and adults with relapsed B ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19012

CD-19 CAR-T cell therapy in adult B-cell ALL patients 1-year overall survival (OS) was 71% in patients treated with KTE-X19, 61% with Obe-cel, 56% with UCART19, and 85.7% with GC007g. Incidence of ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2333/532142/Real-World-Outcomes-of-CD19-Targeted-CAR-T-Cell

Real-World Outcomes of CD19-Targeted CAR T-Cell Therapy ... The cumulative incidence of MRD-negative CR at month +3 was 76.9% (71.9-81.1), followed by a 2-year overall survival of 64.6% (58.7-69.8), ...