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

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single center, open-label, phase 1 study to determine the safety and feasibility of infusing CART22-65s with or without huCART19 after administration of lymphodepleting chemotherapy in adult patients with relapsed or refractory B-ALL.

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.

What data supports the effectiveness of the treatment CART22 + huCART19 for Acute Lymphoblastic Leukemia?

Research shows that CAR T-cell therapy targeting CD19, like huCART19, has been very effective in treating B-cell acute lymphoblastic leukemia, especially in younger patients. Additionally, combining targets like CD19, CD20, and CD22 in CAR T-cells has shown promise in overcoming resistance and treating relapsed leukemia, suggesting potential benefits for CART22 + huCART19 treatment. ^{1 2 3 4 5}

Is the CART22 + huCART19 treatment safe for humans?

The CART22 + huCART19 treatment, which involves CAR T cells targeting CD19 and CD22, has shown a favorable safety profile in clinical trials for B-cell acute lymphoblastic leukemia, with no severe toxicities reported. Some patients experienced mild to moderate cytokine release syndrome (a reaction that can cause fever and flu-like symptoms) and rare neurological events, but these were generally manageable and reversible. ^{3 6 7 8 9}

What makes the CART22 + huCART19 treatment unique for acute lymphoblastic leukemia?

The CART22 + huCART19 treatment is unique because it combines two types of engineered T-cells to target leukemia cells, potentially addressing cases where leukemia cells escape detection by traditional CD19-targeting therapies. This dual approach may help overcome resistance and improve treatment outcomes for patients with acute lymphoblastic leukemia. ^{1 3 4 5 10}

Research Team

Noelle Frey

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

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

A cellular antidote to specifically deplete anti-CD19 chimeric antigen receptor-positive cells. [2021]

2. Switzerland 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. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

CAR T in adult ALL: When and for whom? [2022]

4. England pubmed.ncbi.nlm.nih.gov

CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. [2023]

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

Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies. [2022]

7. United States 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. [2022]

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

Relapsed ALL: CAR T vs transplant vs novel therapies. [2022]

9. China pubmed.ncbi.nlm.nih.gov

[Long-term safety and activity of humanized CD19 chimeric antigen receptor T cells for children and young adults with relapsed/refractory acute lymphoblastic leukemia]. [2023]

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

Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL. [2021]