CART22 Therapy for B-Cell Leukemia

Overseen By Brooke Leibfreid

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Hepatitis B, Hepatitis C, HIV, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CART22 cells (a type of cell therapy) to determine its safety and practicality for young people with difficult-to-treat B-cell acute lymphoblastic leukemia. The trial targets those who have relapsed or not responded to previous treatments, such as chemotherapy or bone marrow transplants. Participants must have evidence of this cancer type and have previously tried other treatments without success. The goal is to discover if this novel therapy can offer new hope for those whose cancer persists or recurs despite standard treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, giving participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use systemic steroids or immunosuppressant medications while participating. Inhaled steroids or hydrocortisone for replacement therapy are allowed.

Is there any evidence suggesting that CART22 therapy is likely to be safe for humans?

Research has shown that CART22 cells are safe in studies involving both children and adults. These studies found that the treatment was generally well-tolerated, with manageable side effects. Common side effects included mild to moderate reactions such as fever or tiredness, typical for this kind of therapy. Importantly, the trials showed promising results in helping patients with challenging cases of B-cell acute lymphoblastic leukemia achieve remission. While some side effects may occur, the treatment offers potential benefits for those with limited options. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell acute lymphoblastic leukemia, such as chemotherapy and targeted therapies like tyrosine kinase inhibitors, CART22 therapy offers a novel approach. CART22 involves engineering the patient's own immune cells, specifically T-cells, to better recognize and attack leukemia cells by targeting the CD22 protein found on their surface. This personalized, cellular approach not only aims to enhance the precision and potency of treatment but also holds the promise of reducing long-term side effects often associated with traditional therapies. Researchers are particularly excited about CART22 because it represents a significant step towards more effective and tailored cancer treatments.

What evidence suggests that CART22 therapy might be an effective treatment for B-cell leukemia?

Research has shown that CART22 cells, a type of CAR T cell therapy, may help treat B-cell acute lymphoblastic leukemia (B-ALL). These cells are designed to target and attack the CD22 protein on cancer cells, aiding the immune system in fighting leukemia. In this trial, pediatric patients with B-ALL that has returned or not responded to other treatments will receive CART22 therapy. Early results suggest that CART22-65s cells can sometimes lead to cancer remission. However, more research is needed to fully understand their effectiveness. This treatment is being carefully studied for its potential to help patients with this challenging condition. ^{1 3 4 6 7}

Who Is on the Research Team?

Stephan Grupp, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1-29 with relapsed or refractory B-cell acute lymphoblastic leukemia. Participants must have adequate organ function, documented CD22 tumor expression, and agree to birth control if applicable. Excluded are those with HIV, active hepatitis B/C, certain CNS diseases, use of systemic steroids/immunosuppressants (with exceptions), pregnancy/nursing women, recent investigational drug use.

Inclusion Criteria

My B-cell ALL has returned or didn't respond to treatment.

Signed informed consent form must be obtained prior to any study procedure

Evidence of disease by standard morphologic or by MRD criteria

Exclusion Criteria

Pregnant or nursing (lactating) women

Receipt of a prior investigational study agent within 4 weeks prior to screening visit (exceptions listed)

My brain condition is worsening or increases my risk of brain side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of autologous T cells expressing CD22 chimeric antigen receptors, administered as split fractions over 2-3 days depending on cohort assignment

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of minimal residual disease (MRD) and adverse events

1 year

Regular visits (in-person and virtual)

Long-term follow-up

Participants are monitored for long-term safety and adverse events, including cytokine release syndrome (CRS)

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CART22 cells

Trial Overview

The study tests a single dose of CART22 cells in pediatric patients. These cells are modified T cells engineered to target CD22 on leukemia cells using a special receptor called 'chimeric antigen receptors' with co-stimulatory domains TCRζ/4-1BB.

How Is the Trial Designed?

Group I: Pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

CAR-modified T-cell therapy targeting CD19 has shown impressive remission rates of 50% to 60% at 1 year for patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL), marking a significant advancement in treatment for this challenging condition.

While the therapy is effective, it can lead to side effects such as cytokine release syndrome (CRS) and neurotoxicity shortly after treatment, as well as long-term B-cell aplasia, which are important considerations for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy Clinical Results in Pediatric and Young Adult B-ALL. DiNofia, AM., Maude, SL.[2020]

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has become a significant advancement in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), with two such therapies approved by regulatory agencies.

Despite the success of CD19-targeting CAR T-cells, some patients still experience relapses, highlighting the need for ongoing research into resistance mechanisms and potential strategies to overcome them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia. Saleh, K., Pasquier, F., Bigenwald, C., et al.[2023]

Anti-CD19 CAR T-cell therapy has shown high response rates in treating relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), but many patients experience relapse due to the therapy's limited persistence and tumor escape mechanisms.

The review highlights new CAR targets and strategies to enhance CAR T-cell effectiveness while also addressing serious side effects like cytokine release syndrome and neurotoxicity, aiming to improve patient outcomes in R/R B-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chimeric antigen receptor targets and constructs for acute lymphoblastic leukemia: Moving beyond CD19. Acharya, L., Garg, A., Rai, M., et al.[2023]

In a study of 33 diffuse large B cell lymphoma (DLBCL) patients, low levels of differentiated CD3+CD27-CD28- T cells before CART cell therapy were found to be a strong predictor of overall response and complete remission, suggesting their potential as a biomarker for treatment efficacy.

Despite having similar cytotoxic capabilities, CD3+CD8+ T cells were more effective than CD3+CD4+ T cells in killing CD19+ target cells, highlighting the importance of T cell type in the effectiveness of CART cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The frequency of differentiated CD3+CD27-CD28- T cells predicts response to CART cell therapy in diffuse large B-cell lymphoma. Worel, N., Grabmeier-Pfistershammer, K., Kratzer, B., et al.[2023]

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 study of 42 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), those treated with anti-CD19 CAR T cells showed a complete response (CR) rate of 28% and an overall response rate of 44% after 4 weeks, with a median overall survival of 64 months.

Achieving a complete response was linked to significantly longer overall survival and progression-free survival, indicating that the effectiveness of CAR T cell therapy is enhanced in patients who reach CR, regardless of whether they received a low or high dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia. Frey, NV., Gill, S., Hexner, EO., et al.[2021]

CD22 is a key surface molecule found on most B-cell acute lymphoblastic leukemia (B-ALL) cells, and therapies targeting CD22, like inotuzumab, have shown promising results, with up to 80% of treated patients achieving complete remission.

Current treatments for B-ALL have high relapse rates, but novel immune-targeted therapies may improve outcomes by effectively targeting chemo-refractory cells, suggesting that analyzing CD22 expression could help predict treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD22 Expression in B-Cell Acute Lymphoblastic Leukemia: Biological Significance and Implications for Inotuzumab Therapy in Adults. Lanza, F., Maffini, E., Rondoni, M., et al.[2023]

Chimeric antigen receptor T (CART) cell therapy is effective against relapsed/refractory B-cell hematological cancers but has a high relapse rate due to factors like T-cell exhaustion and the presence of inhibitory receptors.

The mechanisms behind CD19+ relapse include genetic changes in B cells and the presence of CD19 subclones, but these challenges may be addressed with new pharmacological interventions and improved CAR designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of failure of chimeric antigen receptor T-cell therapy. Li, X., Chen, W.[2020]

The novel CD19-specific CAR T cells incorporating CD28 and IL-15Rα (153z CAR) showed superior T cell expansion and prolonged cytotoxic activity against target cells, indicating enhanced therapeutic potential.

A clinical case demonstrated that a patient with acute lymphoblastic leukemia, who had multiple relapses and failed conventional treatments, achieved complete remission after receiving the 153z CAR T cell therapy, suggesting promising efficacy in treating resistant cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Improvement of Chimeric Antigen Receptor Through Intrinsic Interleukin-15Rα Signaling. Nair, S., Wang, JB., Tsao, ST., et al.[2020]

Chimeric antigen receptor T-cell (CART) therapy has achieved impressive complete remission rates of 65% to 90% in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), marking a significant advancement in treatment.

The introduction of CART therapy has also brought new toxicity profiles and treatment challenges, highlighting the need for standardized toxicity grading systems and innovative management strategies to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies. Talleur, AC., Myers, R., Annesley, C., et al.[2022]

In a study involving five pediatric patients who relapsed after CD19-targeted CAR-T therapy, co-administration of CD19- and CD22-targeted CAR-T cells resulted in 100% of patients achieving minimal residual disease-negative complete remission, demonstrating high efficacy as a salvage therapy.

The treatment was found to be safe, with only mild cytokine release syndrome observed and no neurological toxicity, allowing for successful bridging to allogeneic hematopoietic stem cell transplantation in three patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy. Li, W., Ding, L., Shi, W., et al.[2023]

CART19 therapy, which targets CD19, has shown significant success in treating relapsed/refractory B cell acute lymphoblastic leukemia (ALL) in patients aged 25 and younger, making it a standard treatment for this age group.

For older adults, CART19 therapy is more complex and typically only available through clinical trials, requiring careful evaluation of treatment goals, potential for stem cell transplants, and the specific risks and benefits of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T in adult ALL: When and for whom? Connor, MP., Frey, NV.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12007026/

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

This study reports results of parallel phase I trials of a novel CD22 CAR T cell therapy, CART22-65s, in children and adults who experienced ...

2.

lymphoblastic-hub.com

lymphoblastic-hub.com/medical-information/efficacy-and-safety-of-cart22-65s-in-children-and-adults-with-relapsed-b-all-parallel-phase-i-studies

Efficacy and safety of CART22-65s in children and adults ...

We summarize key results from two phase I trials evaluating the efficacy and safety of CART22-65s in children and adults with R/R B-ALL post ...

3.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06711

CART22-65s and huCART19 CAR T Cells for the ...

This phase I/II trial tests the the safety, side effects, best dose and effectiveness of two specific chimeric antigen receptor (CAR) T cells.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02650414

NCT02650414 | CD22 Redirected Autologous T Cells for ALL

This is a pilot study to determine the feasibility and safety of a single dose of autologous T cells expressing CD22 chimeric antigen receptors expressing ...

5.

ashpublications.org

ashpublications.org/bloodadvances/article/9/8/1916/536668/Humanizing-CAR-T-cell-therapy-in-B-ALL

Humanizing CAR T-cell therapy in B-ALL | Blood Advances

The collective data suggest that it is too early to know whether humanized CAR T cells offer benefits over murine constructs in B-ALL. To ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05674175

Co-administration of CART22-65s and huCART19 for B-ALL

The safety of the administering CART22-65s and huCART19 will be measured by the monitoring the frequency and severity of adverse events in patients with ...

7.

pubmed.ncbi.nlm.nih.gov

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

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

Conclusions: The favorable safety profile and high remission rates in exceedingly refractory B-ALL support the continued development of CART22- ...