CART22 + huCART19 for Acute Lymphoblastic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Hepatitis B, Hepatitis C, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 15 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and feasibility of a new treatment for adults with B-cell Acute Lymphoblastic Leukemia (B-ALL) that has returned after treatment or did not respond to initial therapy. Researchers are examining two experimental treatments: one using CART22-65s cells alone and another combining CART22-65s cells with huCART19 cells. This trial suits individuals who have experienced at least two relapses of their leukemia or have not responded to previous treatments, with disease response assessable through imaging or lab tests. 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 new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot have planned concurrent treatment with systemic steroids or immunosuppressant medications, unless it's a stable low dose of steroids for certain conditions.

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

A previous study found CART22-65s cells to be safe for patients with difficult-to-treat B-cell Acute Lymphoblastic Leukemia (B-ALL). Most patients tolerated the treatment well, indicating its safety.

Research has also shown that huCART19 cells are generally safe. Although some patients experienced a severe immune reaction called cytokine release syndrome (CRS), it was manageable.

Overall, earlier studies have shown that both treatments are well-tolerated. These results suggest that the treatments are relatively safe for further testing in new patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CART22-65s and huCART19 cells for treating acute lymphoblastic leukemia (ALL) because they introduce a new way of targeting cancer cells. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, these treatments are engineered T cells that specifically target leukemia cells by recognizing unique proteins on their surface. CART22-65s and huCART19 offer the potential for more precise attacks on cancer cells with possibly fewer side effects. This precision and personalization are what make these treatments stand out from existing options, such as chemotherapy and radiation.

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

Research shows that CART22-65s cells, which participants in this trial may receive as monotherapy, could be promising for treating relapsed or hard-to-treat B-cell acute lymphoblastic leukemia (B-ALL). Previous studies have demonstrated that this treatment can effectively manage the disease in both children and adults. For huCART19 cells, research indicates they can lead to long-lasting improvements, with many patients remaining disease-free for up to two years. In this trial, some participants will receive a combination of CART22-65s and huCART19, which previous studies have found to be both practical and effective, offering a potential new option for patients with difficult-to-treat B-ALL. These findings suggest that these treatments could be powerful tools in fighting the disease. ^{1 2 4 6 7}

Who Is on the Research Team?

Noelle Frey

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults over 18 with B-cell ALL that's come back or hasn't responded to treatment can join. They must have tried a tyrosine kinase inhibitor if they have Ph+ ALL, and their organs must work well. People with CNS3 disease can only join if it's under control.

Inclusion Criteria

My B cell ALL has come back or didn't respond to treatment.

My kidney, liver, and heart functions are within normal ranges.

My cancer cells show CD22 for Cohort 1 or CD22/CD19 for Cohort 2.

Exclusion Criteria

I have active hepatitis B or C.

My brain condition is worsening or increases my risk of brain side effects.

I have had optic neuritis or another immune-related disease affecting my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CAR T cell infusion

1-2 weeks

Treatment

Participants receive CART22-65s with or without huCART19 infusion

15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• CART22-65s cells
• huCART19 Cells

Trial Overview The trial is testing CART22-65s cells alone or combined with huCART19 after chemotherapy to see if they're safe and workable for treating relapsed/refractory B-ALL in adults. It's an early-phase study where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: CART22-65s monotherapy Experimental Treatment 1 Intervention

Group II: CART22-65s in combination with huCART19 Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

CART19 therapy, which targets CD19, has shown significant success in treating relapsed/refractory B cell acute lymphoblastic leukemia (ALL) in patients aged 25 and younger, making it a standard treatment for this age group.

For older adults, CART19 therapy is more complex and typically only available through clinical trials, requiring careful evaluation of treatment goals, potential for stem cell transplants, and the specific risks and benefits of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T in adult ALL: When and for whom? Connor, MP., Frey, NV.[2022]

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-1/2 trial involving 13 adult patients with refractory acute lymphoblastic leukemia, third-generation CAR T cells (CARTs) demonstrated promising efficacy, with 80% of evaluable patients achieving complete remission, including 50% with no detectable residual disease.

The treatment was associated with remarkably low toxicity, as none of the patients experienced severe side effects like neurotoxicity or high-grade cytokine release syndrome, indicating a favorable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. Schubert, ML., Schmitt, A., Hückelhoven-Krauss, A., et al.[2023]

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]

Chimeric antigen receptor T-cell (CART) therapy has achieved impressive complete remission rates of 65% to 90% in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), marking a significant advancement in treatment.

The introduction of CART therapy has also brought new toxicity profiles and treatment challenges, highlighting the need for standardized toxicity grading systems and innovative management strategies to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies. Talleur, AC., Myers, R., Annesley, C., et al.[2022]

In a study of 168 patients with refractory/relapsed B-cell acute lymphoblastic leukemia, those who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) after CAR-T therapy had similar long-term survival rates compared to those who underwent haplo-HSCT after achieving minimal residual disease-negative complete remission from chemotherapy.

Patients who achieved a first complete remission (CR1) after chemotherapy had better overall survival and leukemia-free survival rates than those who had a second or more complete remission (≥CR2), highlighting the importance of achieving an earlier remission for better transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell therapy versus chemotherapy. Yang, TT., Meng, Y., Kong, DL., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12007026/

CD22-targeted chimeric antigen receptor-modified T cells for ... This study reports results of parallel phase I trials of a novel CD22 CAR T cell therapy, CART22-65s, in children and adults who experienced ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05674175

Co-administration of CART22-65s and huCART19 for B-ALL This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute ...

3. lymphoblastic-hub.com lymphoblastic-hub.com/medical-information/efficacy-and-safety-of-cart22-65s-in-children-and-adults-with-relapsed-b-all-parallel-phase-i-studies

Efficacy and safety of CART22-65s in children and adults ... We summarize key results from two phase I trials evaluating the efficacy and safety of CART22-65s in children and adults with R/R B-ALL post ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06711

CART22-65s and huCART19 CAR T Cells for the ... This phase I/II trial tests the the safety, side effects, best dose and effectiveness of two specific chimeric antigen receptor (CAR) T cells.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121024629

CART22-65s Co-Administered with huCART19 in Adult ... Co-administration and adaptive dosing of CART22-65s with huCART19 in adult patients with r/r ALL is feasible and effective.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05674175

Co-administration of CART22-65s and huCART19 for B-ALL This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40246579/

CD22-targeted chimeric antigen receptor-modified T cells for ... Conclusions: The favorable safety profile and high remission rates in exceedingly refractory B-ALL support the continued development of CART22- ...