Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Stanford University
No Placebo Group
Trial Summary
What is the purpose of this trial?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 Antigen Receptor T-Cell Therapy (CART) cells when administered 28 to 42 days after an infusion of a commercial CAR called Tisagenlecleucel, to children and young adults with relapsed or refractory B-cell leukemia.
How is CD22 CAR T-cell treatment different from other treatments for leukemia?
CD22 CAR T-cell treatment is unique because it targets the CD22 protein on leukemia cells, which is often retained even when other targets like CD19 are lost, making it effective for patients who do not respond to CD19-targeted therapies. This treatment involves modifying a patient's own immune cells to better recognize and attack leukemia cells, offering a novel approach for those with resistant forms of the disease.
234711What data supports the effectiveness of the CD22 CAR T Cells treatment for leukemia?
Research shows that CD22 CAR T Cells treatment can lead to remission in patients with acute lymphoblastic leukemia (ALL), especially those who did not respond to previous treatments targeting a different protein (CD19). In one study, 73% of patients achieved complete remission, although the remissions were often short-lived due to changes in the leukemia cells.
123611Will 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 CD22 CAR T-cell therapy safe for humans?
CD22 CAR T-cell therapy has been studied in early phase trials and is generally considered safe, but it can cause side effects like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Severe cases of these side effects are rare, and the therapy's safety profile is similar to other CAR T-cell therapies.
578910Eligibility Criteria
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
My leukemia has returned or didn't respond to treatment.
My condition worsened after a stem cell transplant.
My condition qualifies me for KYMRIAH® treatment as per FDA guidelines.
My cancer cells test positive for CD19 and CD22.
I am between 1 and 25 years old.
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
My white blood cell count is very high or my disease is getting worse quickly.
I do not have HIV, HBV, HCV, or any uncontrolled illness.
I haven't had a heart attack, heart surgery, or unstable heart conditions in the last year.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: LymphodepletionExperimental Treatment2 Interventions
All enrolled participants will receive lymphodepletion followed by standard of care tisagenlecleucel infusion.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Stanford UniversityPalo Alto, CA
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Who is running the clinical trial?
Stanford UniversityLead Sponsor
References
Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infusions of higher numbers of T cells correlated with improved responses.
CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. [2022]Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. Dose-dependent antileukemic activity was observed, with complete remission obtained in 73% (11/15) of patients receiving ≥1 × 106 CD22-CAR T cells per kg body weight, including 5 of 5 patients with CD19dim or CD19- B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted CD22+ cell escape from killing by CD22-CAR T cells. These results are the first to establish the clinical activity of a CD22-CAR in B-ALL, including leukemia resistant to anti-CD19 immunotherapy, demonstrating potency against B-ALL comparable to that of CD19-CAR at biologically active doses. Our results also highlight the critical role played by antigen density in regulating CAR function.
Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence. [2021]Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority of post-CD22 CART remissions are short and associated with reduction in CD22 expression. We evaluate the implications of low antigen density on the activity of CD22 CART and propose mechanisms to overcome antigen escape.
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. [2020]Chimeric antigen receptor T (CAR-T) cell therapy simultaneously against CD19 and CD22 is an attractive strategy to address the antigen escape relapse after CD19-directed CAR-T cell therapies. However, the potential of optimizing the durability of remission by this approach in patients with B cell acute lymphoblastic leukemia (B-ALL) remains a critical unanswered question so far.
Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy. [2020]Chimeric antigen receptor T-cell (CART) therapy can significantly improve outcomes for patients with certain hematologic malignancies. The most notable drawbacks of CART are cytokine release syndrome and CART-related encephalopathy syndrome. Gastrointestinal adverse events (GI-AEs) have not yet been reported in association with CART. Herein, we describe the incidence and clinical features of GI-AEs observed after CART.
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. [2021]Patients with B-cell acute lymphoblastic leukemia who experience relapse after or are resistant to CD19-targeted immunotherapies have limited treatment options. Targeting CD22, an alternative B-cell antigen, represents an alternate strategy. We report outcomes on the largest patient cohort treated with CD22 chimeric antigen receptor (CAR) T cells.
Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]In a phase I trial of chimeric antigen receptor T cells targeting CD19 and CD22 in younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, toxicity was manageable, and five of 12 patients had complete responses.
Reactions Related to CAR-T Cell Therapy. [2021]The application of chimeric antigen receptor (CAR) T-cell therapy as a tumor immunotherapy has received great interest in recent years. This therapeutic approach has been used to treat hematological malignancies solid tumors. However, it is associated with adverse reactions such as, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), off-target effects, anaphylaxis, infections associated with CAR-T-cell infusion (CTI), tumor lysis syndrome (TLS), B-cell dysplasia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) and coagulation disorders. These adverse reactions can be life-threatening, and thus they should be identified early and treated effectively. In this paper, we review the adverse reactions associated with CAR-T cells, the mechanisms driving such adverse reactions, and strategies to subvert them. This review will provide important reference data to guide clinical application of CAR-T cell therapy.
A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. [2023]Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.
Effects of CAR-T Cell Therapy on Immune Cells and Related Toxic Side Effect Analysis in Patients with Refractory Acute Lymphoblastic Leukemia. [2023]To observe the effects of chimeric antigen receptor T (CAR-T) cell immunotherapy on immune cells and related toxic side effects in patients with refractory acute lymphoblastic leukemia (ALL).
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]The efficacy of CD22 or CD19 chimeric antigen receptor T (CAR-T) cells in the management of acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) was observed. Because antigen loss and lack of CAR-T-cell persistence are the leading causes of progressive disease following single-antigen targeting, we evaluated CD22/CD19 dual-targeting CAR-T-cell therapy efficacy and safety in relapsed/refractory B-cell malignancies.