CD22 CAR T Cells for Leukemia

Overseen By Michelle Fujimoto

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Immunosuppressants

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new therapy using CD22 CAR T cells, a type of immunotherapy, to treat children and young adults with B-cell leukemia that has returned or resisted treatment. Researchers aim to determine the safety of this therapy and identify the best dose following an infusion of a standard treatment called Tisagenlecleucel. Participants must have B-cell leukemia that has not responded well to other treatments and must exhibit specific markers (CD19 and CD22) on their cancer cells. Joining this trial could provide a new treatment option for those whose leukemia has returned or resisted standard therapies. 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 new 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, you must meet a washout period (time without taking certain medications) since prior therapies according to commercial KYMRIAH® (tisagenlecleucel) guidelines.

Is there any evidence suggesting that CD22 CAR T Cells are likely to be safe for humans?

Research shows that CD22 CAR T cells, a type of cell therapy tested for leukemia, are promising in terms of safety. Studies with both children and adults have generally shown these treatments to be well-tolerated. Some patients experienced side effects, which can occur with any treatment, but overall, the results are encouraging.

In one review, researchers examined extensive data from various studies on CD22 CAR T cells. They found that the treatment is mostly safe for people whose B-cell leukemia has returned or doesn't respond to other treatments. Another study found that using CD22 CAR T cells with CD19 CAR T cells also had good safety results.

Since this trial is in its early stages, it focuses on checking the treatment's safety and finding the best dose. Early trials often mean less is known about safety, but existing research provides a positive outlook. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD22 CAR T Cells for leukemia because they offer a novel approach to treatment by directly modifying a patient's own immune cells to target and destroy cancer cells. Unlike standard treatments like chemotherapy, which can affect both healthy and cancerous cells, CD22 CAR T Cells are designed to specifically target the CD22 protein found on the surface of leukemia cells. This targeted action potentially reduces harm to healthy cells and may lead to fewer side effects. Additionally, CAR T Cell therapy has the potential to provide long-lasting remission, offering new hope for patients with this challenging condition.

What evidence suggests that CD22 CAR T Cells might be an effective treatment for leukemia?

Research has shown that CD22 CAR T-cell therapy could be promising for treating B-cell leukemia that has returned or hasn't responded to other treatments. In one study, these specially modified immune cells successfully found and attacked cancer cells with the CD22 protein, common in B-cell leukemia. Trials with both children and adults have shown positive results, with some patients achieving remission. Another analysis indicated that these therapies are safe and can lead to lasting improvements. In this trial, all participants will receive lymphodepletion followed by a standard tisagenlecleucel infusion. These findings suggest that CD22 CAR T-cell treatment could offer hope for patients who haven't succeeded with other treatments. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for children and young adults with B-cell leukemia that has come back or hasn't responded to treatment. They must have already received a commercial CAR T cell therapy called tisagenlecleucel.

Inclusion Criteria

I am willing to use birth control during the trial.

My cancer cells test positive for CD19 and CD22.

I am over 16 and can do most activities, or I am 16 or under and can be active more than half the time.

Exclusion Criteria

Severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition

I do not have HIV, HBV, HCV, or any uncontrolled illness.

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 lymphodepletion followed by standard of care tisagenlecleucel infusion

1 week

Treatment

Participants receive CD22 CAR T cells 28 to 42 days after infusion of tisagenlecleucel

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of B cell aplasia

6 months

What Are the Treatments Tested in This Trial?

Interventions

• CD22 CAR T Cells

Trial Overview The study tests the safety and optimal dosing of CD22 CART cells given 28 to 42 days after tisagenlecleucel in patients with relapsed or refractory B-cell leukemia.

How Is the Trial Designed?

Group I: Lymphodepletion Experimental Treatment 2 Interventions

All enrolled participants will receive lymphodepletion followed by standard of care tisagenlecleucel infusion.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

Chimeric antigen receptor T-cell (CART) therapy targeting CD22 is effective in inducing remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL), but many remissions are short-lived due to reduced CD22 expression on leukemic cells.

Using Bryostatin1 to upregulate CD22 expression significantly enhances CART functionality and persistence, leading to longer-lasting responses in vivo, despite some reduction in IFNγ production by CART.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence. Ramakrishna, S., Highfill, SL., Walsh, Z., et al.[2021]

In a phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.

Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

In a study involving 58 children and young adults with relapsed or refractory B-cell malignancies, CD22-targeted CAR T cells achieved a complete remission rate of 70%, demonstrating significant efficacy as an alternative treatment for patients who did not respond to CD19-targeted therapies.

The treatment was generally safe, with most side effects being mild to moderate, although cytokine release syndrome occurred in 86.2% of participants, indicating the need for careful monitoring and potential toxicity management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial. Shah, NN., Highfill, SL., Shalabi, H., et al.[2021]

In a phase 1 trial involving 21 patients, including 17 who had previously undergone CD19-targeted therapy, a new CD22-targeted CAR T cell therapy showed a complete remission rate of 73% in patients receiving sufficient doses (≥1 × 10^6 CD22-CAR T cells per kg).

The study highlights that while CD22-CAR T cells are effective against B-ALL, relapses were linked to lower CD22 site density, indicating that the density of target antigens plays a crucial role in the effectiveness of CAR T cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Fry, TJ., Shah, NN., Orentas, RJ., et al.[2022]

A first-in-human trial of anti-CD22 CAR T-cell therapy in children and young adults with relapsed acute lymphocytic leukemia demonstrated that the treatment is feasible, safe, and effective, resulting in remissions for most patients.

The study found that infusing higher numbers of T cells was associated with better treatment responses, suggesting a dose-dependent effect in the therapy's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]

A patient with relapsed and refractory B cell acute lymphoblastic leukemia (B-ALL) achieved over 14 months of minimal residual disease-negative remission after receiving CAR-T cell therapy targeting both CD19 and CD22.

This case suggests that dual-targeting CAR-T cell therapy may enhance the durability of remission in B-ALL patients, potentially addressing issues of antigen escape seen with single-target therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical CD19/CD22 bispecific CAR-T cells induced MRD-negative remission in a patient with relapsed and refractory adult B-ALL after haploidentical hematopoietic stem cell transplantation. Jia, H., Wang, Z., Wang, Y., et al.[2020]

In a study of 132 patients receiving chimeric antigen receptor T-cell (CART) therapy, 28% experienced gastrointestinal adverse events (GI-AEs), primarily diarrhea, with a median onset of 7 days after treatment.

While most GI-AEs were mild and self-limiting, there were cases of more severe symptoms, including refractory colitis in one patient, highlighting the need for monitoring and management of these potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy. Abu-Sbeih, H., Tang, T., Ali, FS., et al.[2020]

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]

CAR T-cell therapy is a promising treatment for various cancers, including hematological malignancies and solid tumors, but it can lead to serious adverse reactions such as cytokine release syndrome (CRS) and neurotoxicity.

Understanding the mechanisms behind these adverse reactions is crucial for early identification and effective treatment, which is essential for the safe clinical application of CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactions Related to CAR-T Cell Therapy. Miao, L., Zhang, Z., Ren, Z., et al.[2021]

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 35 patients with refractory acute lymphoblastic leukemia (ALL), CAR-T cell therapy demonstrated a high total effective rate of 91.43%, with 68.57% achieving complete response after one month of treatment.

The therapy was associated with significant changes in immune cell populations, including a decrease in regulatory T cells and an increase in natural killer cells, while side effects were generally mild and manageable, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of CAR-T Cell Therapy on Immune Cells and Related Toxic Side Effect Analysis in Patients with Refractory Acute Lymphoblastic Leukemia. Li, L., Gao, J., Sun, Z., et al.[2023]

Citations

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

A systematic review and meta-analysis of CD22 CAR T-cells ... This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies.

2. 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.

3. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.19.03279

Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial We report outcomes on the largest patient cohort treated with CD22 chimeric antigen receptor (CAR) T cells. Patients and Methods. We ...

4. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00316-0/fulltext

Tandem CD19/CD22 CAR T-cells as potential therapy for ... Chimeric antigen receptor (CAR) T-cells targeting CD19 have shown impressive outcomes in refractory/relapsed B-cell acute lymphoblastic ...

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

Autologous CD22 Chimeric Antigen Receptor (CAR) T ... This phase I trial tests the safety, side effects and feasibility of giving autologous CD22 chimeric antigen receptor (CAR) T cells followed by commercial CD19 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40246579/

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

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

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