CAR T Cells for Lymphoma

Overseen By Kelly Chyan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must be taking: Anti-CD20 antibody

Must not be taking: Immunosuppressants

Disqualifiers: Other malignancies, Active infections, Cardiac disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a non-randomized clinical trial to evaluate the safety and efficacy of CD22CART administered after lymphodepleting chemotherapy in adults with relapsed / refractory B Cell Lymphomas. All evaluable participants will be followed for overall survival (OS), progression free survival (PFS), and duration of response (DOR). An evaluable participant is one who completes leukapheresis, lymphodepleting chemotherapy and CART infusion.

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, there are required 'washout' periods (time without taking certain medications) before certain procedures, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment CD22CART for lymphoma?

Research shows that CD22-targeting CAR T-cell therapies have high remission rates in certain blood cancers like acute lymphoblastic leukemia and non-Hodgkin's lymphoma, with a best complete response rate of 64% in NHL. This suggests potential effectiveness for similar conditions. ^{1 2 3 4 5}

Is CD22-directed CAR T-cell therapy safe for humans?

CD22-directed CAR T-cell therapy has been studied for safety in humans, showing that severe side effects like cytokine-release syndrome (CRS) and neurotoxicity are rare. Most patients experience mild to moderate side effects, and dual-targeting with CD19 does not increase toxicity. ^{1 3 4 6 7}

How is CD22CART treatment different from other treatments for lymphoma?

CD22CART is a unique treatment for lymphoma because it targets the CD22 protein on cancer cells, which can be effective for patients who do not respond to or relapse after CD19-targeting therapies. This approach offers an alternative for those with relapsed or refractory B-cell malignancies, potentially improving outcomes by addressing antigen loss that can occur with other treatments. ^{1 2 3 4 5}

Research Team

Matthew Frank, PhD, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults with certain types of B Cell Lymphomas that have come back or haven't responded to treatment. Participants must have tried at least two prior therapies, including one with an anti-CD20 monoclonal antibody and chemotherapy. They should not be eligible if they've had fewer than two previous lines of therapy or don't meet specific disease progression criteria.

Inclusion Criteria

I have completed the necessary waiting period after my last treatment before starting leukapheresis.

My blood, kidney, liver, lung, and heart functions are within normal ranges.

Baseline oxygen saturation > 92% on room air ANC Platelet ALC Cr CreatCl AST/ALT Bilirubin LVEF O2 Sat

Exclusion Criteria

May NOT, in investigator's judgment, have any medical condition likely to interfere with assessment of safety or efficacy, or be likely to complete all protocol-required visits and procedures

My condition is worsening quickly and may stop me from finishing the treatment.

Is pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants undergo lymphodepleting chemotherapy prior to CD22CART infusion

1-2 weeks

CD22CART Infusion

Participants receive the CD22CART infusion after lymphodepleting chemotherapy

1 day

Follow-up

Participants are monitored for safety and effectiveness after CD22CART infusion

3 months

Long-term Follow-up

Participants are followed for overall survival, progression free survival, and duration of response

6 years

Treatment Details

Interventions

• CD22CART

Trial Overview The trial tests CD22CART Infusion after lymphodepleting chemotherapy in patients with relapsed/refractory B Cell Lymphomas. It aims to assess the safety and effectiveness by tracking overall survival, progression-free survival, and duration of response post-treatment.

Participant Groups

Group I: Cohort 3: Other lymphomas Experimental Treatment 1 Intervention

up to 30 participants with no more than 10 of any one type, including: Hairy cell leukemia, Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia), Burkitt lymphoma, and Marginal zone lymphoma.

Group II: Cohort 2: Mantle cell lymphoma (MCL) Experimental Treatment 1 Intervention

12-32 participants with MCL will be administered the RP2D of CD22CART.

Group III: Cohort 1: Follicular lymphoma (FL) Experimental Treatment 1 Intervention

18-34 participants with FL will be administered the RP2D of CD22CART

CD22CART is already approved in United States for the following indications:

Approved in United States as CD22-directed CAR T-cell therapy for:

• Relapsed/Refractory Large B-Cell Lymphoma

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+

Findings from Research

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]

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]

A novel T-cell receptor (TCR) targeting the CD22-derived peptide was identified, showing promise for treating B-cell malignancies by effectively recognizing and killing leukemia cells while sparing most healthy cells.

TCR-engineered T-cells demonstrated the ability to selectively target CD22-positive B-cell leukemia, suggesting a complementary approach to existing CAR and antibody therapies, although the presence of CD22 on some non-B-cells may pose challenges for this strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute lymphoblastic leukemia by TCR gene transfer. Jahn, L., Hagedoorn, RS., van der Steen, DM., et al.[2018]

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 study successfully engineered CAR-NK-92 cells (m971-BBZ) to target CD22, a protein commonly found on B cell lymphoma, demonstrating their ability to effectively kill these cancer cells in vitro.

The m971-BBZ NK-92 cells not only showed strong cytotoxic effects against CD22-expressing lymphoma cells but also produced significant amounts of cytokines, indicating a robust immune response, while maintaining lower levels of inhibitory receptors compared to CAR-T cells, suggesting a potentially safer profile for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of B cell lymphoma with CD22-redirected CAR NK-92 cells. Tian, X., Zhang, R., Qin, H., et al.[2023]

References

1. 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]

2. 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]

3. 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]

4. 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]

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

A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute lymphoblastic leukemia by TCR gene transfer. [2018]

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. Poland pubmed.ncbi.nlm.nih.gov

Immunotherapy of B cell lymphoma with CD22-redirected CAR NK-92 cells. [2023]