CAR T-Cell Therapy for Acute Lymphoblastic Leukemia

Not currently recruiting at 2 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Seattle Children's Hospital

Must not be taking: Systemic corticosteroids

Disqualifiers: Active CNS dysfunction, Severe infection, Others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with acute lymphoblastic leukemia who have not responded to traditional chemotherapy. The treatment uses CAR T cells (Patient Derived CD19 specific CAR T cells also expressing an EGFRt), which are specially modified immune cells designed to target and destroy leukemia cells. Participants in Phase 1 must have already undergone a bone marrow transplant, while Phase 2 is open to all eligible patients. This trial suits individuals with CD19-positive leukemia who have relapsed or not responded to previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic corticosteroids (unless it's a small dose for hormone replacement) at least 7 days before enrolling. You also need to be off immunosuppressive therapy for graft-versus-host disease (GVHD) for 4 weeks before enrolling. Other medications might need to be paused, but the protocol doesn't specify all details.

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

Research has shown that CD19-specific CAR T-cell therapy is generally safe for patients with leukemia that has returned or not responded to treatment. In one study, patients tolerated the treatment well, experiencing manageable nerve-related side effects. Another study found that a low dose of this therapy was both effective and safe for 51 patients with acute lymphoblastic leukemia. Additionally, similar treatments using donor cells have been safe for patients whose leukemia returned after a stem cell transplant.

These findings suggest that the treatment is mostly well-tolerated, though, like any medical treatment, some side effects may occur. The studies provide promising evidence of safety for those considering joining a trial like this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CAR T-cell therapy for acute lymphoblastic leukemia because it offers a personalized approach by using the patient's own immune cells to target and destroy cancer cells. Unlike traditional chemotherapy, which attacks both healthy and cancerous cells, this therapy specifically targets the CD19 protein found on leukemia cells, potentially reducing side effects. Additionally, the CAR T-cells are engineered to express an EGFRt, which helps control their activity, providing a safety switch to manage adverse reactions. This innovative mechanism promises more precise and effective treatment options compared to current standards.

What evidence suggests that this treatment might be an effective treatment for acute lymphoblastic leukemia?

Research shows that CD19 CAR T-cell therapy effectively treats acute lymphoblastic leukemia (ALL), especially in patients who have relapsed or not responded to other treatments. Studies have shown promising results, with significant improvements in survival rates, even for those who have had bone marrow transplants. In this trial, participants will receive different doses of Patient Derived CD19 specific CAR T cells. Some cohorts will receive low-dose therapy, which has proven both effective and safe, with many entering remission. Another study found that combining CD19 with another target, CD22, led to long-term survival benefits. These findings suggest that CAR T-cell therapy could be a strong option for treating challenging cases of leukemia. ^{2 6 7 8 9}

Who Is on the Research Team?

Colleen Annesley, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young patients (12 months to less than 27 years old) with CD19+ leukemia that's come back or hasn't responded to treatment. They must weigh at least 10kg, have no severe active infections, and not have had certain prior treatments like genetically modified cell therapy. Those who've had a transplant can join phase 1; others may join phase 2.

Inclusion Criteria

Patient must have documented negative HIV antigen and antibody, Hepatitis B surface antigen, and Hepatitis C antibody within 3 months prior to enrollment

Total bilirubin </3x ULN OR conjugated bilirubin </2mg/dl

ALT </5X ULN

Exclusion Criteria

I do not have a severe infection or fever above 38.2 C recently.

Patients must NOT have any concurrent medical condition that, in the opinion of the PI or designee, would prevent the patient from undergoing protocol-based therapy

Patients with a primary immunodeficiency/ bone marrow failure syndrome are excluded from this trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and T Cell Generation

Subjects undergo apheresis to obtain T cells, which are then genetically modified to express CD19 CAR and expanded over a three-week period.

3 weeks

Treatment

Participants receive an infusion of CAR+ T cells following lymphodepletion, if necessary.

2 months

Intense follow-up with serial blood testing and disease status re-evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment, with bi-annual follow-ups for 5 years and annual follow-ups for 10 additional years.

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Trial Overview The study tests CAR T cells made from the patient's own immune cells, engineered to target CD19 on leukemia cells. It aims to find the safest dose and see how well it works. Phase 1 involves post-transplant patients; phase 2 is open more broadly.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 1 Intervention

The phase 2 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1 x 10\^6 CAR T cells/kg following lymphodepletion if indicated.

Group II: Phase 1 - Cohort 1F2 Experimental Treatment 1 Intervention

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^6 CAR T cells/kg following prescribed lymph-depletion with fludarabine and cyclophosphamide

Group III: Phase 1 - Cohort 1F1 Experimental Treatment 1 Intervention

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^5 CAR T cells/kg following prescribed lymph-depletion with fludarabine and cyclophosphamide

Group IV: Phase 1 - Cohort 1D Experimental Treatment 1 Intervention

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^7 CAR T cells/kg

Group V: Phase 1 - Cohort 1C Experimental Treatment 1 Intervention

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^6 CAR T cells/kg

Group VI: Phase 1 - Cohort 1B Experimental Treatment 1 Intervention

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^6 CAR T cells/kg

Group VII: Phase 1 - Cohort 1A Experimental Treatment 1 Intervention

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^5 CAR T cells/kg

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

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 II trial involving 225 patients aged 20 and under, coadministration of CD19- and CD22-CAR T cells resulted in a remarkable 99% complete remission rate for those with refractory B-acute lymphoblastic leukemia, with a 12-month event-free survival (EFS) rate of 73.5%.

While the treatment was effective, it was associated with significant side effects, including cytokine release syndrome in 88% of patients and CAR T-cell neurotoxicity in 20.9%, leading to three deaths, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial. Wang, T., Tang, Y., Cai, J., et al.[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]

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]

CD19/20/22 CAR T-cells have been developed to effectively target B-lineage acute lymphoblastic leukemia (BL-ALL) that has relapsed with CD19(-) disease, showing efficacy in both laboratory and animal models.

These CAR T-cells maintain their effectiveness against CD19(+) disease while also being able to kill CD19(-) blasts, suggesting they could serve as a new treatment option for patients who do not respond to traditional CD19-targeting therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression. Fousek, K., Watanabe, J., Joseph, SK., et al.[2022]

The study found that Tn/mem-derived CD19-CAR T cells were safe and effective in treating adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), with 87% of participants achieving complete remission or partial remission.

Among the 46 participants treated, those with Philadelphia-like ALL and extramedullary disease showed high response rates, and undergoing allogeneic hematopoietic cell transplantation after treatment significantly improved relapse-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable Activity and Safety Profile of Memory-Enriched CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy in Adults with High-Risk Relapsed/Refractory ALL. Aldoss, I., Khaled, SK., Wang, X., et al.[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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10585987/

Outcomes of Second Anti-CD19 CAR T-Cell Therapy ... High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

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

Clinical outcomes of a new local CD19 CAR-T cell therapy ... High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

3. 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 ...

4. haematologica.org haematologica.org/article/view/11872

Five-year outcome of CD19 followed by CD22 chimeric ... Our study revealed that, in post-HCT relapsed B-ALL patients, the combination of CD19 and CD22 CAR T-cell therapy significantly improved long-term survival.

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

CAR T-cells for T-cell acute lymphoblastic leukemia Sixteen clinical studies evaluated the safety and efficacy of DD CAR T-cells targeting CD19 in B-ALL with promising results. 203 patients were included with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11022988/

Efficacy and safety of CD19-specific CAR T cell–based ... Neurotoxicity of CD19 CAR T-cell therapy was acceptable in patients with relapsed/refractory B-ALL with CNSL. •. CD19-specific CAR T cells could induce similar ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5876/527644/Use-of-CD19-CAR-T-Cells-in-Adult-B-Cell-Acute

Use of CD19 CAR-T Cells in Adult B-Cell Acute Lymphoblastic ... CD19 CAR-T cell therapy results in durable remissions for approximately 20-30% of adult and 40-50% of pediatric patients with relapsed/ ...

8. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00554-0/fulltext

Donor-derived Anti-CD19 CAR T cells GC007g for ... Our study findings provide support for the safety and efficacy of donor-derived CAR-T cells in patients who relapsed after allo-HSCT, which ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265020310168

Systematic Review and Meta-analysis of CD19-Specific ... In this systematic review, we analyzed pediatric data and found that CD19 CAR-T therapy can result in CR in RR–B-ALL. Also, the remission is sustained until ...