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

148 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called CD22CART, a type of CAR T-cell therapy, for adults with certain types of B Cell Lymphomas that have returned or resisted treatment. Researchers aim to determine the safety and effectiveness of this treatment after patients undergo chemotherapy to lower their immune system. The trial includes different groups for specific types of lymphoma, such as follicular lymphoma and mantle cell lymphoma. Participants must have a confirmed diagnosis of one of these lymphomas and have previously tried other treatments without success. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

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.

Is there any evidence suggesting that CD22CART is likely to be safe for humans?

Research has shown that CD22CART therapy is generally safe for people with various types of lymphomas. In studies involving follicular lymphoma (FL) and mantle cell lymphoma (MCL), the treatment did not cause severe side effects in the six patients tested. Impressively, five of these six patients experienced a complete response, meaning their cancer disappeared after treatment.

Another study found that all four patients treated responded positively, with no major side effects reported. For those with large B-cell lymphoma (LBCL) who relapsed after previous CAR T-cell therapy, CD22CART also led to complete remission in three patients without causing severe side effects.

These findings suggest that CD22CART treatment has been well-tolerated in early testing and has shown promising results for different types of lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about CD22CART because it offers a novel approach for treating lymphomas through CAR T-cell therapy. Unlike standard treatments like chemotherapy and radiation, which attack cancer cells more broadly, CD22CART specifically targets the CD22 protein on the surface of cancerous B cells. This precision allows for potentially more effective and less toxic treatment. Additionally, CD22CART has the potential to provide lasting remission by harnessing the body's immune system to fight cancer, which is a significant advancement over traditional therapies.

What evidence suggests that CD22CART might be an effective treatment for lymphoma?

Research has shown that CD22-directed CAR T-cell therapy, known as CD22CART, holds promise for treating various types of lymphoma. In this trial, participants with follicular lymphoma will receive CD22CART. Studies have found that all patients responded to the treatment, with 83% achieving complete remission. Participants with mantle cell lymphoma will also receive CD22CART, which has helped patients who did not improve with other CAR T-cell therapies achieve complete remission. For those with large B-cell lymphoma, CD22CART has resulted in long-term remissions, even for those who relapsed after other treatments. Overall, CD22CART has been very effective in achieving remission for these lymphoma types, with few severe side effects reported. ^{1 2 3 4 6}

Who Is on the Research Team?

Matthew Frank, PhD, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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

Is pregnant or breastfeeding

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Cohort 4: Relapsed/refractory large B cell lymphoma (LBCL) Experimental Treatment 1 Intervention

14 - 19 participants will be administered the RP2D of CD22 CART

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

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

Group IV: 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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2064/529883/CD22-Directed-CAR-T-Cell-Therapy-Achieves-Complete

CD22-Directed CAR T-Cell Therapy Achieves Complete ... CD22-directed CAR T-cell therapy achieves complete remission in CD19-directed CAR T-cell refractory follicular and mantle cell lymphoma.

2. astctjournal.org astctjournal.org/article/S2666-6367(25)00627-X/fulltext

CD22-Directed CAR T-Cell Therapy Achieves Complete ... CAR22 therapy in FL & MCL is safe with no observed DLTs in all 6 patients. Efficacy is promising with 5 of 6 high-risk, CAR-exposed patients achieving CR.

3. 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.

4. 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 ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/car22-therapy-safe-and-effective-in-mcl-follicular-lymphoma

CAR22 Therapy Safe and Effective in MCL, Follicular ... CAR22 therapy demonstrated an ORR of 100% and a complete response rate of 83% in six patients with MCL or follicular lymphoma.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S266663672500627X

CD22-Directed CAR T-Cell Therapy Achieves Complete ... CAR22 therapy in FL & MCL is safe with no observed DLTs in all 6 patients. Efficacy is promising with 5 of 6 high-risk, CAR-exposed patients achieving CR.