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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CD22 CAR T-cell therapy for individuals with certain B-cell cancers, such as leukemia and lymphoma, that have returned or are difficult to treat. The goal is to determine if these modified immune cells, created from a patient's own cells, can effectively target cancer cells. The trial includes two main groups: one for those with relapsed or stubborn acute lymphoblastic leukemia (ALL) and another for aggressive B-cell non-Hodgkin lymphoma. Suitable candidates are those who have tried at least two other treatments for these cancers without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CD22 CAR T-cell therapy is generally well-tolerated in people with B-cell cancers. Studies have found that CAR T-cells, which are special immune cells modified in a lab to fight cancer, can be effective with usually manageable side effects.

Trials testing both CD22 and CD19 dual-targeting CAR T-cells demonstrated high effectiveness while maintaining side effects at a tolerable level. This indicates that while some side effects may occur, they are typically not severe enough to outweigh the potential benefits of the treatment.

It is important to note that this trial is in an early phase. Treatments at this stage primarily focus on ensuring safety and identifying any side effects. The current testing of CD22 CAR T-cells indicates that while earlier research has shown promise, their safety and side effects are still under close observation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for B-cell cancers, like chemotherapy and radiation, work by killing rapidly dividing cells. But CD22 CAR T-cell therapy works differently, targeting the CD22 protein on the surface of cancerous B-cells. This means it offers a more precise attack, potentially leading to fewer side effects compared to traditional treatments. Researchers are excited about this therapy because it uses the body's own immune cells, modified to better recognize and destroy cancer cells, which could lead to more effective and lasting responses for patients with relapsed or refractory B-cell cancers.

What evidence suggests that this trial's treatments could be effective for B-cell cancers?

Research has shown that CD22 CAR T-cell therapy, which participants in this trial may receive, may effectively treat relapsed or hard-to-treat acute lymphoblastic leukemia (r/r ALL). One study found that 74% of patients achieved complete remission, although some later experienced a return of the disease. For aggressive B-cell non-Hodgkin lymphoma (r/r aggressive B-cell NHL), CD22 CAR T-cell therapy is under investigation in this trial. Although still in early stages, the results suggest it could be a promising treatment for these challenging cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew Frank, PhD, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31110217/

CD22 CAR T-cell therapy in refractory or relapsed B acute ...

Our study demonstrated that our CD22 CAR T-cells was highly effective in inducing remission in r/r B-ALL patients, and also provided a precious window for ...

2.

nature.com

nature.com/articles/s41375-019-0488-7

CD22 CAR T-cell therapy in refractory or relapsed B acute ...

A recent study showed that CD22 CAR T-cell therapy in 21 r/r B-ALL patients resulting in a 74% CR rate, but most patients relapsed after CD22 ...

3.

haematologica.org

haematologica.org/article/view/11872

Five-year outcome of CD19 followed by CD22 chimeric ...

Our study revealed that, in post-HCT relapsed B-ALL patients, the combination of CD19 and CD22 CAR T-cell therapy significantly improved long-term survival.

4.

ehoonline.biomedcentral.com

ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00593-5

Prominent efficacy and good safety of sequential CD19 and ...

This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between ...

5.

jitc.bmj.com

jitc.bmj.com/content/13/4/e011549

CD22-targeted chimeric antigen receptor-modified T cells ...

We tested a novel, fully human anti-CD22/4-1BB CAR T-cell construct, CART22-65s, in parallel phase I studies for pediatric and adult B-ALL.

6.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/4510/534000/Preliminary-Safety-and-Tolerability-of-CD19x22-CAR

Preliminary Safety and Tolerability of CD19x22 CAR-T Cell ...

Efficacy and Safety of CD19-Targeted CAR-T Cell Therapy for Refractory/Relapsed B-Cell Lymphoma: A Single Center of Real World Data. Jing ...

7.

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.

8.

thelancet.com

thelancet.com/journals/lancet/article/PIIS0140-6736(24)00746-3/fulltext

CD22-directed CAR T-cell therapy for large B- ...

Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 (CAR19) have improved outcomes for relapsed or refractory large B-cell lymphoma.

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06081478

CD19/CD22 Bispecific CAR-T Cell Therapy for Relapsed ...

In this prospective phase 2 clinical trial, we aim to explore the efficacy and safety of CD19/CD22 bispecific CAR-T cell therapy in relapsed/refractory B-ALL or ...

10.

translational-medicine.biomedcentral.com

translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06567-3

Efficacy and safety of a novel CD19, CD22 dual-targeted ...

Overall, CT120 infusion is effective, safe, and reliable for reducing antigen escape-related relapse in patients with relapsed or refractory NHL.