Dual-Targeted CAR-T Therapy for Leukemia

Not currently recruiting at 5 trial locations

Overseen By Colleen Annesley, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Disqualifiers: CNS dysfunction, Pregnancy, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain types of leukemia when other treatments have failed. It uses a special T-cell therapy, where T-cells (a type of immune cell) are taken from the patient and modified to attack leukemia cells with both CD19 and CD22 proteins. This approach is known as Patient-derived CD19- and CD22-specific CAR-T Cell Immunotherapy. The main goal is to determine the treatment's safety and whether enough modified T-cells can be produced for treatment. Individuals with leukemia that has CD19 and CD22 proteins and who have struggled with previous treatments might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance 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, you must be free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks before enrolling, and at least 7 days post last chemotherapy and systemic corticosteroids administration.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dual-targeted CAR-T therapy, which targets both CD19 and CD22 proteins on leukemia cells, has been safe in earlier studies. These studies found the treatment effective, with manageable side effects for patients with B-cell cancers.

In a study conducted in Spain, patients who received this dual-targeted CAR-T therapy experienced an acceptable safety profile, with no severe side effects. Another analysis demonstrated that treatments targeting CD22 alone or both CD19 and CD22 had good safety results for blood cancers.

Overall, current data suggests this dual-targeted approach is well-tolerated. However, as this trial is in its early stages, the primary goal is to further evaluate the treatment's safety for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the dual-targeted CAR-T therapy for leukemia because it offers a novel approach by using patient-derived CAR-T cells that target both CD19 and CD22. Unlike standard treatments that often focus on a single target, this therapy aims to reduce the likelihood of cancer cells escaping detection by the immune system. Additionally, the therapy incorporates engineered receptors, HER2t and EGFRt, which may enhance the precision and effectiveness of the immune response against cancer cells. This multi-target strategy has the potential to improve outcomes by tackling the disease from multiple angles simultaneously.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that dual-targeted CAR-T therapy, which targets the proteins CD19 and CD22, can effectively treat leukemia. This trial will test two versions of the therapy: "Patient-derived CD19- and CD22 specific CAR v1" and "Patient-derived CD19- and CD22 specific CAR v2." By targeting both proteins, this therapy helps prevent cancer recurrence by stopping cancer cells from hiding. One study found that patients who received this treatment had a 70% chance of survival over 18 months. Another study confirmed that this approach is effective and has manageable side effects for B-cell cancers. These findings suggest that this treatment could benefit patients with leukemia that has returned or is difficult to treat. ^{1 2 6 7 8}

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 patients under 31 years old with CD19+CD22+ leukemia that's resistant to standard treatments. They must have a life expectancy of at least 8 weeks, be free from severe infections or CNS dysfunction, not pregnant or breastfeeding, and able to tolerate cell collection procedures. Participants should also meet certain health and laboratory criteria.

Inclusion Criteria

I am under 31 years old.

Patients of childbearing/fathering potential must agree to use highly effective contraception from the time of initial T cell infusion through 12 months following the last T cell infusion

My cancer has returned or didn't respond to treatment, and I haven't had a stem cell transplant.

Exclusion Criteria

Presence of any concurrent medical condition that, in the opinion of the Principal Investigator, would prevent the patient from undergoing protocol-specified therapy

I have significant brain or nerve problems affecting my daily life.

I cannot undergo apheresis due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive genetically modified T-cells expressing CD19 and CD22 CARs to target leukemia cells

4 weeks

Multiple visits for T-cell infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after CAR T-cell infusion

4 weeks

Regular visits for monitoring adverse events and treatment response

What Are the Treatments Tested in This Trial?

Interventions

• Patient-derived CD19- and CD22-specific CAR-T Cell Immunotherapy

Trial Overview The study tests a new therapy using the patient's own T-cells genetically modified to target two proteins on leukemia cells (CD19 and CD22). It aims to see if this dual-targeting approach is safe and feasible in producing enough modified T-cells for treatment.

How Is the Trial Designed?

Group I: Patient-derived CD19- and CD22 specific CAR v2 Experimental Treatment 1 Intervention

Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt

Group II: Patient-derived CD19- and CD22 specific CAR v1 Experimental Treatment 1 Intervention

Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt

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 study of 16 patients with relapsed/refractory aggressive B-cell lymphoma, bispecific CAR T cells targeting both CD19 and CD22 showed a high efficacy, with 87.5% achieving an objective response and 62.5% achieving complete response.

The treatment demonstrated a favorable safety profile, with only one patient experiencing severe cytokine-release syndrome, and no cases of neurotoxicity, suggesting that this dual-targeted approach may be a safe and effective option for lymphoma therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19/CD22 Dual-Targeted CAR T-cell Therapy for Relapsed/Refractory Aggressive B-cell Lymphoma: A Safety and Efficacy Study. Wei, G., Zhang, Y., Zhao, H., et al.[2022]

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

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]

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]

The CD22/CD19 dual-targeting CAR-T-cell therapy showed a remarkable overall response rate of 97% and a complete remission rate of 93% in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), based on a meta-analysis of 14 studies involving 405 patients.

For non-Hodgkin lymphoma (NHL), the therapy resulted in an overall response rate of 85% and a complete remission rate of 57%, with manageable side effects such as cytokine release syndrome occurring in 86% of patients, indicating both efficacy and tolerability of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis. Nguyen, TT., Thanh Nhu, N., Chen, CL., et al.[2023]

In a phase 1 trial involving 15 pediatric and young adult patients with relapsed or refractory B-ALL, the dual-targeting CAR T-cell therapy AUTO3 demonstrated a favorable safety profile with no severe toxicities reported and an impressive remission rate of 86% one month post-treatment.

Despite the high initial remission rate, the one-year overall survival rate was 60% and event-free survival rate was 32%, indicating that improvements in the persistence of AUTO3 CAR T-cells are necessary to enhance long-term outcomes and prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Cordoba, S., Onuoha, S., Thomas, S., et al.[2022]

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]

The development of dual-targeting CAR T cells that target both CD19 and BAFF-R shows promise in overcoming treatment failures due to antigen loss in B-cell malignancies, specifically acute lymphoblastic leukemia (ALL).

In preclinical studies, these dual CAR T cells effectively eradicated both CD19- and BAFF-R-negative ALL variants in mice, demonstrating superior efficacy compared to single-target CAR T cells and suggesting potential for durable remissions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia. Wang, X., Dong, Z., Awuah, D., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12049870/

CD22 CAR-T cells secreting CD19 T-cell engagers for ... CD22 CAR-T cells secreting CD19 T-cell engagers show an enhanced control of B-ALL progression compared with CD19/CD22 dual CAR-based therapies, ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5877/527643/Long-Term-Outcomes-and-Adverse-Events-of-CAR-T-19

Long-Term Outcomes and Adverse Events of CAR T-19 Cell ... The combination of CD19 and CD22 targeting CAR T-cells further enhances efficacy, addressing antigen escape. Despite high efficacy, significant ...

3. haematologica.org haematologica.org/article/view/11872

Five-year outcome of CD19 followed by CD22 chimeric ... Regarding the long-term survival after CD19 CAR T-cell therapy, recent investigations showed an EFS of 44% and OS of 63% at 3 years in young adult and pediatric ...

4. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00316-0/fulltext

Tandem CD19/CD22 CAR T-cells as potential therapy for ... At the 18-month follow up, overall survival (OS) was 70% (95% CI, 47%–100%). Interpretation. Tandem anti-CD19/CD22 CAR T-cell administration ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10557829/

Effectiveness and safety of CD22 and CD19 dual‐targeting ... Our meta‐analysis demonstrated that the CD22/CD19 dual‐targeting CAR‐T‐cell strategy has high efficiency with tolerable adverse effects in B‐cell malignancies.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2352396425003160

Tandem CD19/CD22 CAR T-cells as potential therapy for ... We report Spanish clinical data on the safety and efficacy of tandem anti-CD19/CD22 CAR T-cells administered on a compassionate use basis in a cohort of 10 ...

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

Efficacy and safety of CD19-specific CAR T cell–based ... Our results suggest that CD19-specific CAR T cell–based therapy can induce similar high response rates in both BM and CNS diseases. The duration of remission in ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.954345/full

Efficacy and safety of CD22-specific and CD19 ... Both CD22 and CD19/CD22 CAR-T immunotherapy demonstrated favorable efficacy and acceptable adverse events in the treatment of hematologic malignancies.