CD22-CAR T Cells for B-Cell Cancer

Overseen By Michael Kunicki

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from pediatric and young adult subjects with relapsed/refractory B-cell malignancies (leukemia and lymphoma). Another purpose of this study is to test the safety and cancer killing ability of a cell therapy against a new cancer target (CD22).

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) of at least 2 weeks or 5 half-lives, whichever is shorter, for most prior treatments before starting the study. Some medications, like inotuzumab ozogamicin for ALL, require a longer period of 4 months. If you're on standard ALL maintenance chemotherapy, you must stop at least 1 week or 5 half-lives before starting the study.

What data supports the effectiveness of the treatment Autologous CD22 CAR T for B-Cell Cancer?

Research shows that CD22 CAR T-cells have high remission rates in certain B-cell cancers like acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), with complete response rates of 68% in ALL and 64% in NHL. This suggests that CD22 CAR T-cells can be effective, especially for patients who have not responded to other treatments. ^{1 2 3 4 5}

Is CD22-CAR T cell therapy safe for humans?

CD22-CAR T cell therapy has been tested in clinical trials and is generally considered safe, with some patients experiencing mild to moderate side effects like cytokine release syndrome (CRS, a reaction that can cause fever and low blood pressure) and neurotoxicity (nerve-related side effects). Severe side effects are rare, and dual-targeting with CD19 does not seem to increase toxicity. ^{1 3 4 6 7}

How is the CD22-CAR T cell treatment different from other treatments for B-cell cancer?

CD22-CAR T cell treatment is unique because it targets the CD22 antigen on B cells, which can be an alternative when patients do not respond to or relapse after CD19-CAR T cell therapy. This treatment uses a patient's own modified immune cells to attack cancer cells, offering a novel approach for those who have not benefited from existing therapies. ^{1 2 3 4 8}

Research Team

Liora Schultz, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for children and young adults with certain types of B-cell cancers, like leukemia and lymphoma, that haven't responded to at least two previous treatments. They must have measurable signs of cancer despite treatment or a confirmed return of the disease after remission. Those with specific genetic changes in their leukemia are also eligible.

Inclusion Criteria

My lymphoma has worsened or returned after treatment for a different type.

My ALL can be measured or seen through tests.

My cancer returned in the brain or spinal cord after it was previously gone.

Exclusion Criteria

Unlikely to complete all protocol required study visits or procedures

I have an ongoing infection with HIV, hepatitis B, or hepatitis C.

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 a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide

5 days

Daily visits for chemotherapy administration

Treatment

Infusion of CD22 CAR T cells

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Regular visits for monitoring response and safety

Treatment Details

Interventions

• Autologous CD22 CAR T

Trial Overview The study is testing a new cell therapy using CD22-CAR T cells made from the patient's own immune cells. It aims to see if these cells can be created successfully and whether they're safe and effective at targeting and killing cancer cells in patients with relapsed or resistant B-cell malignancies.

Participant Groups

Group I: R/R B-ALL Experimental Treatment 3 Interventions

Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).

Group II: Lymphoma Experimental Treatment 3 Interventions

Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

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]

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]

This systematic review aims to evaluate the efficacy and safety of CD22-targeting CAR T cell therapies in treating relapsed or refractory B cell malignancies, addressing the issue of patients who do not respond to CD19-targeting therapies.

The review will analyze various clinical trials, focusing on complete response rates and adverse events, to provide a comprehensive understanding of CD22 CAR T cell therapies and guide future research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell malignancies: a protocol for a systematic review and meta-analysis. Adeel, K., Fergusson, NJ., Shorr, R., et al.[2021]

In a study of 13 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and B cell acute lymphoid leukemia (B-ALL) who previously failed anti-CD19 CAR T cell therapy, anti-CD22 CAR T cell salvage therapy resulted in a higher complete response rate in DLBCL patients, with 4 achieving complete response compared to only 2 in B-ALL.

The anti-CD22 CAR T cell therapy was associated with lower grades of cytokine release syndrome (CRS) compared to the previous anti-CD19 therapy, indicating a potentially safer profile, while overall survival for DLBCL patients was approximately 6.1 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy. Zhu, H., Deng, H., Mu, J., et al.[2022]

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]

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. 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]

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

B cell targeting in CAR T cell therapy: Side effect or driver of CAR T cell function? [2022]

3. 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]

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

Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell malignancies: a protocol for a systematic review and meta-analysis. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy. [2022]

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

Nanobody-based anti-CD22-chimeric antigen receptor T cell immunotherapy exhibits improved remission against B-cell acute lymphoblastic leukemia. [2022]