CD22-CAR T Cells for B-Cell Cancer

Overseen By Michael Kunicki

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Immunosuppressants, Antimicrobials

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: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called CD22-CAR T cells to determine its safety and effectiveness in treating B-cell cancers, such as leukemia and lymphoma, in children and young adults who haven't responded to other treatments. The goal is to assess whether these modified immune cells can target and kill cancer cells with the CD22 protein. Individuals who have not succeeded with standard treatments and have experienced a relapse might be suitable candidates for this study. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that CD22 CAR T cells are generally safe for both children and adults with certain B-cell cancers. In earlier studies, these treatments helped some patients achieve complete remission without severe side effects. While some side effects might occur, they are usually not serious. One study found that patients did not experience major negative reactions after receiving CD22 CAR T cells. Overall, early research suggests that CD22 CAR T cells are generally well-tolerated in people with relapsed or difficult-to-treat B-cell cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the use of CD22 CAR T cells for B-cell cancers because they offer a unique, personalized approach that differs from traditional treatments like chemotherapy and monoclonal antibodies. Unlike these standard treatments, CD22 CAR T therapy involves engineering a patient's own T cells to specifically target and destroy cancer cells that express the CD22 protein. This targeted approach has the potential to be more effective and less toxic, as it aims to hone in directly on cancer cells while sparing healthy ones. Additionally, CAR T cell therapy has shown promise in producing durable remissions, giving hope for longer-term control of these challenging cancers.

What evidence suggests that CD22-CAR T cells might be an effective treatment for B-cell cancer?

Research has shown that CD22 CAR T-cell therapy can help treat certain B-cell cancers. In this trial, participants with large B-cell lymphoma will receive CD22 CAR T-cell therapy, which led to complete remission in some studies for patients who had relapsed after other treatments. This means their cancer was no longer detectable after receiving the therapy. Additionally, participants with B-cell acute lymphoblastic leukemia (B-ALL) who did not respond to standard chemotherapy will also receive CD22 CAR T cells. Previous studies have shown promise, with nearly half achieving complete remission. These findings suggest that CD22 CAR T-cell therapy might offer hope for those with hard-to-treat B-cell cancers. ^{1 2 4 6 7}

Who Is on the Research Team?

Liora Schultz, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

Citations

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

CD22-directed CAR T-cell therapy for large B- ... Outcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8085484/

CD22-directed CAR T-cell therapy induces complete ... CAR22 therapy induced complete remission in 3 patients with LBCL who had relapsed after CAR19 therapy and caused no severe toxicities.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324925008503

Outcomes following CD22 CAR T-cells in B-ALL: a tale of ... Data from a pre-clinical study, in which GD2 CAR T-cells were manufactured using three different platforms, demonstrated clear differences, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04163575

Immunotherapy With CD22 CAR T-cells for B ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10174241/

A systematic review and meta-analysis of CD22 CAR T-cells ... Among patients with B-cell acute lymphoblastic leukemia (B-ALL) who have failed standard induction chemotherapy, only 45% achieve complete ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-04331

Autologous CD22 Chimeric Antigen Receptor (CAR) T ... Giving CD22CART followed by commercial CD19CART cell may be safe and tolerable in treating children and young adults with recurrent or refractory ALL.

7. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/a/NCT06408194.html

Autologous CD22 CAR T Cells Following Commercial CD19 ... 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 ...