CD22 CAR T-Cell Therapy for B-Cell Cancers

Overseen By Maria Iglesias

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Immunosuppressants

Disqualifiers: Infections, Cardiac disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

52 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol requires a washout period (time without taking certain medications) of at least 2 weeks or 5 half-lives, whichever is shorter, for most prior systemic therapies before starting the trial. However, some medications like hydroxyurea and certain maintenance chemotherapies have specific guidelines, so it's best to discuss your current medications with the trial team.

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

Research shows that CD22 CAR T-Cell treatment has high remission rates in certain B-cell cancers, like acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL), with complete response rates of 68% in ALL and 64% in NHL. This treatment is especially promising for patients who did not respond to or relapsed after CD19 CAR T-Cell therapy. ^{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 for B-cell cancers like acute lymphocytic leukemia and non-Hodgkin's lymphoma. While most patients experienced some level of cytokine release syndrome (CRS, a reaction where the immune system becomes overly active), severe cases were rare. Neurotoxicity (problems with the nervous system) was also uncommon, suggesting that the therapy is generally safe, though more research is needed for long-term safety outcomes. ^{1 2 4 6 7}

How is CD22 CAR T-cell therapy different from other treatments for B-cell cancers?

CD22 CAR T-cell therapy is unique because it targets the CD22 antigen on B-cells, offering an alternative for patients who do not respond to or relapse after CD19-targeted therapies. This approach helps address the issue of antigen loss, which can occur with CD19 therapies, and provides a new option for treating B-cell cancers. ^{1 2 4 5 8}

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 adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma).

Research Team

Matthew Frank, PhD, MD

Principal Investigator

Stanford University

Eligibility Criteria

Adults over 18 with certain B-cell blood cancers that have come back or didn't respond to treatment. They must be able to consent, not pregnant, willing to use birth control, and meet specific health criteria like a minimum number of white blood cells and proper organ function. Can't join if they're pregnant/breastfeeding, have other cancers within 3 years, severe infections needing IV drugs, significant heart issues in the past year or conditions affecting study participation.

Inclusion Criteria

I had chemotherapy with anthracycline before my cancer changed its type.

Ability to give informed consent

My leukemia or aggressive B-cell lymphoma can be measured or evaluated.

Exclusion Criteria

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

I am currently being treated with IV drugs for an infection.

I have been cancer-free from another type of cancer for over 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion with Fludarabine and Cyclophosphamide prior to CD22 CAR T cell infusion

3 days

3 visits (in-person)

Treatment

Participants receive CD22 CAR T cell infusion at varying dose levels to determine MTD/RP2D

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• CD22 CAR
• Cyclophosphamide
• Fludarabine

Trial Overview The trial is testing CD22-CAR T cells made from patients' own immune cells against relapsed/refractory B-cell malignancies. It includes pre-treatment with Fludarabine and Cyclophosphamide which are chemotherapy drugs used to prepare the body for CAR T cell therapy.

Participant Groups

Group I: R/R aggressive B-cell NHL Experimental Treatment 3 Interventions

Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D. Dose1: 1 x 10\^6 cells/kg (± 20%) Dose2: 3 x 10\^6 cells/kg (± 20%) Dose3: 1 x 10\^7 cells/kg (± 20%)

Group II: R/R ALL Experimental Treatment 3 Interventions

Relapsed/refractory ALL Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10\^5cells/kg (± 20%) 10

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

American Society of Hematology

Collaborator

Trials

14

Recruited

20,800+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 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]

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]

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]

Anti-CD19 CAR-modified T cells have demonstrated a 48% overall response rate in treating B-cell malignancies, with complete responses observed in 24% of patients across six phase I clinical trials involving 50 patients.

The study found that conditioning chemotherapy significantly improves progression-free survival (PFS), making it a crucial factor for enhancing the efficacy of CAR T-cell therapy, while the treatment was generally well tolerated with temporary adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. Zhu, Y., Tan, Y., Ou, R., et al.[2022]

References

1. 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]

2. 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]

3. 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]

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

B cell targeting in CAR T cell therapy: Side effect or driver of CAR T cell function? [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. England pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Targeting CD22 for B-cell hematologic malignancies. [2023]