CAR T-cell Therapy for Acute Lymphoblastic Leukemia

Overseen By Vanessa Fabrizio, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Disqualifiers: CNS leukemia, Severe organ dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for children and young adults with acute lymphoblastic leukemia (ALL) that has returned or not responded to other treatments. It focuses on CD19x22 Chimeric Antigen Receptor T-cell Therapy, a type of CAR T-cell therapy that uses modified immune cells to target cancer. Researchers aim to determine if this treatment is safe and well-tolerated. This trial may suit those whose ALL has returned at least twice or has not responded to other treatments and who have the specific cancer markers CD19 and/or CD22. 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 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.

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

Research has shown that CD19/CD22 dual-targeting CAR T-cell therapy is generally well-tolerated. A review of several studies found this treatment effective, with manageable side effects in B-cell cancers. A study from Spain provided clinical data demonstrating the treatment's safety and success in compassionate cases. Although some side effects may occur, these studies suggest the treatment is generally safe for patients. However, as this is an early-phase trial, the primary goal is to determine the safest dose and understand any potential side effects. While the treatment appears promising, much remains to be learned about its safety in this specific use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Acute Lymphoblastic Leukemia, which typically involve chemotherapy and targeted therapy, CD19x22 CAR T-cell therapy uses a unique approach by reprogramming a patient's own immune cells to target and attack cancer cells. This treatment is distinctive because it combines two targets, CD19 and CD22, on cancer cells, potentially increasing the chances of eliminating the leukemia. Researchers are excited about this therapy because it harnesses the body's natural defenses, aiming for a powerful and precise attack on the cancer, which might lead to longer-lasting remissions and fewer side effects compared to conventional treatments.

What evidence suggests that CD19x22 CAR T-cell therapy might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that a new CAR T-cell therapy, targeting both CD19 and CD22 proteins, effectively treats certain blood cancers like acute lymphoblastic leukemia (ALL). In this trial, participants will receive the CD19x22 Chimeric Antigen Receptor T-cell Therapy. A review of several studies found this method effective with manageable side effects. By targeting both CD19 and CD22, this therapy can help prevent cancer recurrence, which often occurs when only CD19 is targeted, as cancer cells can lose CD19. This dual-targeting approach aims to reduce the risk of cancer cells escaping treatment. Early results are promising, particularly for difficult cases that haven't responded to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Vanessa Fabrizio, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for children with a type of blood cancer called B-ALL that has come back or hasn't responded to treatment. Participants should meet specific health conditions, but the exact criteria aren't provided here.

Inclusion Criteria

Provision of signed consent form from appropriate party

Willingness to comply with study procedures and long-term follow-up protocol

I have had B-cell acute lymphoblastic leukemia with a specific type of relapse.

Exclusion Criteria

I have HIV or active Hepatitis B/C.

I am a woman who has gone through puberty and have a pregnancy-related condition.

I have leukemia in my brain that is not under control.

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 week

Treatment

Participants receive CD19x22 CAR T cell therapy with dose escalation based on body weight

4 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• CD19x22 Chimeric Antigen Receptor T-cell Therapy

Trial Overview The study tests a new therapy where T-cells (a type of immune cell) are engineered to target and kill leukemia cells by recognizing two proteins, CD19 and CD22, on their surface.

How Is the Trial Designed?

Group I: Low Disease Burden Cohort Experimental Treatment 1 Intervention

\<25% bone marrow lymphoblasts and no non-CNS extramedullary disease. Dose escalation will proceed independently within each cohort using the Bayesian Optimal Interval (BOIN)design. Dose begins at DL1 (3x10\^5 cells/kg).

Group II: High Disease Burden Cohort Experimental Treatment 1 Intervention

≥25% bone marrow lymphoblasts and/or non-CNS extramedullary disease. Dose escalation will proceed independently within each cohort using the Bayesian Optimal Interval (BOIN)design. Dose begins at DL -1(1x10\^5 cells/kg).

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

In a phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.

Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

CD22-targeting CAR T-cell therapies show high complete response rates, with 68% in acute lymphoblastic leukemia (ALL) and 64% in non-Hodgkin's lymphoma (NHL), indicating their efficacy in treating these malignancies.

The incidence of severe side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), is low, suggesting that these therapies are relatively safe, especially with dual-targeting CAR T-cells not increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. Fergusson, NJ., Adeel, K., Kekre, N., et al.[2023]

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]

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]

A patient with relapsed and refractory B cell acute lymphoblastic leukemia (B-ALL) achieved over 14 months of minimal residual disease-negative remission after receiving CAR-T cell therapy targeting both CD19 and CD22.

This case suggests that dual-targeting CAR-T cell therapy may enhance the durability of remission in B-ALL patients, potentially addressing issues of antigen escape seen with single-target therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical CD19/CD22 bispecific CAR-T cells induced MRD-negative remission in a patient with relapsed and refractory adult B-ALL after haploidentical hematopoietic stem cell transplantation. Jia, H., Wang, Z., Wang, Y., et al.[2020]

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]

CD19 CAR T-cell therapy has shown a high complete remission rate in pediatric acute lymphoblastic leukemia, highlighting its efficacy as a treatment for this type of cancer.

Despite its effectiveness, CD19 CAR T-cell therapy is associated with significant adverse reactions and an increased risk of cancer recurrence, necessitating further research into mechanisms of recurrence and strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cluster of differentiation 19 chimeric antigen receptor T-cell therapy in pediatric acute lymphoblastic leukemia. Fu, Z., Zhou, J., Chen, R., et al.[2020]

In a phase 1 trial involving 21 patients, including 17 who had previously undergone CD19-targeted therapy, a new CD22-targeted CAR T cell therapy showed a complete remission rate of 73% in patients receiving sufficient doses (≥1 × 10^6 CD22-CAR T cells per kg).

The study highlights that while CD22-CAR T cells are effective against B-ALL, relapses were linked to lower CD22 site density, indicating that the density of target antigens plays a crucial role in the effectiveness of CAR T cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Fry, TJ., Shah, NN., Orentas, RJ., et al.[2022]

In a study involving 58 children and young adults with relapsed or refractory B-cell malignancies, CD22-targeted CAR T cells achieved a complete remission rate of 70%, demonstrating significant efficacy as an alternative treatment for patients who did not respond to CD19-targeted therapies.

The treatment was generally safe, with most side effects being mild to moderate, although cytokine release syndrome occurred in 86.2% of participants, indicating the need for careful monitoring and potential toxicity management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial. Shah, NN., Highfill, SL., Shalabi, H., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06559189

CD19x22 Chimeric Antigen Receptor T-cell Therapy (CAR ... This study will evaluate the safety and tolerability of administering a novel bispecific CD19/CD22-directed CAR T cell product (CD19x22) for the treatment of ...

2. 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.

3. nature.com nature.com/articles/s41591-021-01436-0

CAR T cells with dual targeting of CD19 and CD22 in adult ... Disease progression associated with loss of cell surface CD19 has been reported in 30–95% of relapses after CAR19 therapy in B-ALL, through a ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06242

CD19x22 CAR T Cells for the Treatment of Pediatric ... This phase I trial tests the safety, side effects, best dose, and effectiveness of CD19x22 chimeric antigen receptor (CAR) T cells in treating pediatric ...

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

Tandem CD19/CD22 CAR T-cells as potential therapy for ... Chimeric antigen receptor (CAR) T-cells targeting CD19 have shown impressive outcomes in refractory/relapsed B-cell acute lymphoblastic ...