CD22 CAR T Cells for Leukemia

Overseen By Michelle Fujimoto

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Immunosuppressants

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must meet a washout period (time without taking certain medications) since prior therapies according to commercial KYMRIAH® (tisagenlecleucel) guidelines.

What data supports the effectiveness of the CD22 CAR T Cells treatment for leukemia?

Research shows that CD22 CAR T Cells treatment can lead to remission in patients with acute lymphoblastic leukemia (ALL), especially those who did not respond to previous treatments targeting a different protein (CD19). In one study, 73% of patients achieved complete remission, although the remissions were often short-lived due to changes in the leukemia cells. ^{1 2 3 4 5}

Is CD22 CAR T-cell therapy safe for humans?

CD22 CAR T-cell therapy has been studied in early phase trials and is generally considered safe, but it can cause side effects like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Severe cases of these side effects are rare, and the therapy's safety profile is similar to other CAR T-cell therapies. ^{6 7 8 9 10}

How is CD22 CAR T-cell treatment different from other treatments for leukemia?

CD22 CAR T-cell treatment is unique because it targets the CD22 protein on leukemia cells, which is often retained even when other targets like CD19 are lost, making it effective for patients who do not respond to CD19-targeted therapies. This treatment involves modifying a patient's own immune cells to better recognize and attack leukemia cells, offering a novel approach for those with resistant forms of the disease. ^{3 4 5 9 11}

What is the purpose of this trial?

The primary purpose of this study is to determine safety, feasibility, and the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of CD22 Chimeric Antigen Receptor T-Cell Therapy (CART) cells when administered 28 to 42 days after an infusion of a commercial CAR called Tisagenlecleucel, to children and young adults with relapsed or refractory B-cell leukemia.

Eligibility Criteria

This trial is for children and young adults with B-cell leukemia that has come back or hasn't responded to treatment. They must have already received a commercial CAR T cell therapy called tisagenlecleucel.

Inclusion Criteria

I am willing to use birth control during the trial.

My cancer cells test positive for CD19 and CD22.

I am over 16 and can do most activities, or I am 16 or under and can be active more than half the time.

Exclusion Criteria

Severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition

I do not have HIV, HBV, HCV, or any uncontrolled illness.

My white blood cell count is very high or my disease is getting worse quickly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive lymphodepletion followed by standard of care tisagenlecleucel infusion

1 week

Treatment

Participants receive CD22 CAR T cells 28 to 42 days after infusion of tisagenlecleucel

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of B cell aplasia

6 months

Treatment Details

Interventions

• CD22 CAR T Cells

Trial Overview The study tests the safety and optimal dosing of CD22 CART cells given 28 to 42 days after tisagenlecleucel in patients with relapsed or refractory B-cell leukemia.

Participant Groups

Group I: Lymphodepletion Experimental Treatment 2 Interventions

All enrolled participants will receive lymphodepletion followed by standard of care tisagenlecleucel infusion.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

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]

A first-in-human trial of anti-CD22 CAR T-cell therapy in children and young adults with relapsed acute lymphocytic leukemia demonstrated that the treatment is feasible, safe, and effective, resulting in remissions for most patients.

The study found that infusing higher numbers of T cells was associated with better treatment responses, suggesting a dose-dependent effect in the therapy's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]

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]

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]

Chimeric antigen receptor T-cell (CART) therapy targeting CD22 is effective in inducing remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL), but many remissions are short-lived due to reduced CD22 expression on leukemic cells.

Using Bryostatin1 to upregulate CD22 expression significantly enhances CART functionality and persistence, leading to longer-lasting responses in vivo, despite some reduction in IFNγ production by CART.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence. Ramakrishna, S., Highfill, SL., Walsh, Z., et al.[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]

In a study of 132 patients receiving chimeric antigen receptor T-cell (CART) therapy, 28% experienced gastrointestinal adverse events (GI-AEs), primarily diarrhea, with a median onset of 7 days after treatment.

While most GI-AEs were mild and self-limiting, there were cases of more severe symptoms, including refractory colitis in one patient, highlighting the need for monitoring and management of these potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy. Abu-Sbeih, H., Tang, T., Ali, FS., et al.[2020]

In a study of 35 patients with refractory acute lymphoblastic leukemia (ALL), CAR-T cell therapy demonstrated a high total effective rate of 91.43%, with 68.57% achieving complete response after one month of treatment.

The therapy was associated with significant changes in immune cell populations, including a decrease in regulatory T cells and an increase in natural killer cells, while side effects were generally mild and manageable, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of CAR-T Cell Therapy on Immune Cells and Related Toxic Side Effect Analysis in Patients with Refractory Acute Lymphoblastic Leukemia. Li, L., Gao, J., Sun, Z., et al.[2023]

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]

CAR T-cell therapy is a promising treatment for various cancers, including hematological malignancies and solid tumors, but it can lead to serious adverse reactions such as cytokine release syndrome (CRS) and neurotoxicity.

Understanding the mechanisms behind these adverse reactions is crucial for early identification and effective treatment, which is essential for the safe clinical application of CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactions Related to CAR-T Cell Therapy. Miao, L., Zhang, Z., Ren, Z., et al.[2021]

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]

References

1. United States 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. [2021]

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

Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]

3. United States 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. [2022]

4. United States 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. [2023]

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

Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence. [2021]

6. Switzerland 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. [2023]

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

Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy. [2020]

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

Effects of CAR-T Cell Therapy on Immune Cells and Related Toxic Side Effect Analysis in Patients with Refractory Acute Lymphoblastic Leukemia. [2023]

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

Reactions Related to CAR-T Cell Therapy. [2021]

11. England 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. [2020]