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

Trial Summary

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.

What data supports the effectiveness of the treatment CD19-CAR T cell for Acute Lymphoblastic Leukemia?

CD19-CAR T cell therapy has shown high initial success rates, with complete remission in up to 90% of patients with relapsed or chemotherapy-resistant B-cell acute lymphoblastic leukemia, compared to a 30% response rate with chemotherapy. However, long-term remission is achieved in 40% to 50% of patients, indicating its potential but also the need for further improvements. ^{1 2 3 4 5}

Is CAR T Cell Therapy for Acute Lymphoblastic Leukemia safe for humans?

CAR T Cell Therapy, including CD19-CAR T cells, has been tested in clinical trials and shown to cause side effects like cytokine release syndrome (CRS) and neurotoxicity, which can be serious but are generally manageable with treatments like tocilizumab and corticosteroids. While severe side effects are less common in real-world settings due to better management, the therapy is considered to have a tolerable safety profile with careful monitoring. ^{6 7 8 9 10}

How is CD19-CAR T cell treatment different from other treatments for acute lymphoblastic leukemia?

CD19-CAR T cell treatment is unique because it uses genetically engineered T cells to specifically target and attack leukemia cells, offering a novel approach compared to traditional chemotherapy. This treatment can lead to high response rates in patients who have not responded to other therapies, although it may cause severe side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). ^{1 8 11 12 13}

What is the purpose of this trial?

CAR19PK is a research study evaluating the use of lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T cell therapy, a type of cellular therapy, for the treatment of refractory and/or relapsed leukemia. For this type of therapy, peripheral (circulating) immune cells are collected and then modified so that they can recognize an antigen, which is a particle present on the surface of a cancer cell. The CD19-CAR T cell product will be manufactured at the St. Jude Children's Research Hospital's Good Manufacturing Practice (GMP) facility. The main purpose of this study is to determine: * Evaluate different doses of fludarabine prior CAR T cell infusion * How your body processes fludarabine and cyclophosphamide, * How long the CAR T cells last in the body, * Whether or not treatment with this therapy is effective in treating people with refractory or relapsed leukemia, and * The side effects of this therapy.

Research Team

Aimee Talleur, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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, 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]

References

1. United States 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. [2023]

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

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

3. China 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. [2022]

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

Universal CAR T Cells Treat Leukemia. [2017]

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

Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. [2023]

6. England 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). [2020]

7. Japan pubmed.ncbi.nlm.nih.gov

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

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

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. [2021]

10. United States 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. [2022]

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

Allogeneic Donor-Derived Anti-CD19 CAR T Cell Is a Promising Therapy for Relapsed/Refractory B-ALL After Allogeneic Hematopoietic Stem-Cell Transplantation. [2021]

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

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Beyond CD19: Opportunities for Future Development of Targeted Immunotherapy in Pediatric Relapsed-Refractory Acute Leukemia. [2022]