CAR T-cell Therapy for Acute Lymphoblastic Leukemia

(ACIT001/EXC002 Trial)

Recruiting at 5 trial locations

Overseen By Zack Breckenridge

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Alberta

Must not be taking: Corticosteroids, others

Disqualifiers: CNS involvement, HIV, Hepatitis, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

63 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-cell therapy for individuals with certain blood cancers, such as acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma. The goal is to determine if these specially modified immune cells can fight cancer by targeting a protein called CD19 on cancer cells. Suitable candidates have tried at least two other treatments without success and have either ALL or non-Hodgkin's lymphoma that recurs. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any investigational drug or anti-cancer therapy within 30 days, and you must not be on therapeutic doses of corticosteroids within 7 days prior to blood collection for CAR T-cell product manufacture.

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

Research shows that a treatment using a patient's own modified immune cells, called CAR T-cells, has been studied in people with certain B-cell cancers, such as non-Hodgkin lymphoma, that have recurred or are difficult to treat. In these studies, some patients experienced side effects, but the treatment was generally well-tolerated. Common side effects included a strong immune response and some neurological effects, often manageable with proper care. Additionally, similar treatments, like tisagenlecleucel, have received FDA approval for other conditions, indicating a certain level of safety. While new treatments always carry some risk, past patients demonstrated that these therapies can be safely administered with careful monitoring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute lymphoblastic leukemia (ALL), which often include chemotherapy and stem cell transplants, CAR T-cell therapy is unique because it uses a patient's own immune cells. Researchers are excited about this treatment because it involves engineering these T-cells to specifically target and destroy cancer cells by recognizing a protein called CD19 on their surface. This targeted approach not only promises to be more effective for patients with relapsed or refractory B-cell ALL but also offers the potential for fewer side effects compared to traditional therapies. The personalized nature of CAR T-cell therapy represents a groundbreaking shift in how we approach cancer treatment.

What evidence suggests that this treatment might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that a treatment using a patient's own modified immune cells, called autologous CD19-directed CAR T-cells, holds promise for certain blood cancers. In this trial, participants will receive this type of CAR T-cell therapy. For instance, a similar treatment named Kymriah proved very effective for patients with B-cell acute lymphoblastic leukemia (ALL), helping many achieve remission, where the cancer becomes undetectable. Another treatment, YESCARTA, showed positive results for patients with large B-cell lymphoma, improving survival rates. These therapies work by altering the patient's T-cells to specifically attack cancer cells with the CD19 protein. Early evidence suggests these treatments could be powerful options for B-cell cancers that have returned or are not responding to other treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Michael Chu, MD

Principal Investigator

Cross Cancer Institute

Are You a Good Fit for This Trial?

This trial is for people aged 2-70 with CD19+ non-Hodgkin's lymphoma or ALL who've had at least two prior treatments and aren't eligible for curative therapies. They must have a measurable lesion, adequate organ function, and agree to use effective contraception. Exclusions include unresolved toxicities from past treatments, uncontrolled illnesses, recent major surgery, certain infections like HIV or hepatitis B/C, recent vaccinations, pregnancy/breastfeeding, some prior immunotherapies or gene therapies.

Inclusion Criteria

I am a man who can father a child and agree to use birth control during and for 3 months after the study.

I have a measurable tumor or signs of cancer in my blood or bone marrow.

I am between 2 and 70 years old.

Exclusion Criteria

I haven't taken high doses of steroids (more than 20 mg/day of prednisone or equivalent) in the last 7 days.

Received any investigational drug/anti-cancer therapy within 30 days.

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine on Days -5, -4, and -3

1 week

CAR T-cell Administration

Participants receive a single dose of CAR T-cells intravenously on Day 0

1 day

Follow-up

Participants are monitored for safety and effectiveness after CAR T-cell administration

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• autologous CD19-directed chimeric antigen receptor (CAR) T-cells

Trial Overview The trial tests autologous CAR T-cells targeting CD19 on cancer cells in patients with aggressive lymphoma or ALL. These T-cells are modified outside the body using a lentiviral vector to recognize and attack cancer cells before being reintroduced into the patient.

How Is the Trial Designed?

Group I: CAR T cells Experimental Treatment 1 Intervention

Patients with relapsed/refractory B-cell ALL or NHL.

autologous CD19-directed chimeric antigen receptor (CAR) T-cells is already approved in United States, European Union for the following indications:

Approved in United States as Tisagenlecleucel for:

• B-cell precursor acute lymphoblastic leukemia (B-ALL)
• Large B-cell lymphoma (LBCL)

Approved in United States as Lisocabtagene maraleucel for:

• Large B-cell lymphoma (LBCL)
• Diffuse large B-cell lymphoma (DLBCL)
• Transformed indolent lymphoma
• High-grade B-cell lymphoma (HGBCL)
• Primary mediastinal B-cell lymphoma (PMBCL)
• Follicular lymphoma grade 3B

Approved in United States as Axicabtagene ciloleucel for:

• Large B-cell lymphoma (LBCL)
• Diffuse large B-cell lymphoma (DLBCL), transformed indolent lymphoma, high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma grade 3B

Approved in United States as Brexucabtagene autoleucel for:

• Mantle cell lymphoma (MCL)

Approved in European Union as Tisagenlecleucel for:

• B-cell precursor acute lymphoblastic leukemia (B-ALL)
• Large B-cell lymphoma (LBCL)

Approved in European Union as Lisocabtagene maraleucel for:

• Large B-cell lymphoma (LBCL)
• Diffuse large B-cell lymphoma (DLBCL)
• Transformed indolent lymphoma
• High-grade B-cell lymphoma (HGBCL)
• Primary mediastinal B-cell lymphoma (PMBCL)
• Follicular lymphoma grade 3B

Approved in European Union as Axicabtagene ciloleucel for:

• Large B-cell lymphoma (LBCL)
• Diffuse large B-cell lymphoma (DLBCL), transformed indolent lymphoma, high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma grade 3B

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Alberta Cancer Foundation

Collaborator

Trials

18

Recruited

5,600+

Published Research Related to This Trial

The FDA has approved tisagenlecleucel, the first anti-CD19 CAR T-cell therapy, specifically for treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia (ALL).

CAR T-cell therapy, particularly with tisagenlecleucel, shows promise as a standard treatment option for patients with B-cell malignancies, although it has primarily been developed through small clinical studies and poses unique management challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia. Thomas, X., Paubelle, E.[2019]

CAR T cell therapy, specifically with tisagenlecleucel and axicabtagene ciloleucel, has been authorized in Europe for treating certain types of blood cancers, showing efficacy in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.

The recommendations provided focus on managing medium-term complications like cytopenias and B-cell aplasia, emphasizing the importance of supportive care for patients undergoing this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medium-term follow-up of patients treated with chimeric antigen receptor T cells (CAR T cells): Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Alsuliman, T., Drieu La Rochelle, L., Campidelli, A., et al.[2022]

In a study of 79 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia, those who responded to the CAR T-cell therapy tisagenlecleucel showed approximately double the expansion of the therapy in their blood compared to nonresponders, indicating a strong correlation between cellular expansion and treatment efficacy.

The therapy demonstrated persistence in responders for over two years, and its expansion continued even after treatment with tocilizumab, which is used to manage cytokine release syndrome, suggesting that tisagenlecleucel can remain effective despite potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia. Mueller, KT., Waldron, E., Grupp, SA., et al.[2020]

The study found that high levels of leukemia blast contamination in the starting material did not negatively impact the manufacturing of CAR T-cells or their ability to expand, suggesting that CAR T-cell therapy can be safely produced even from contaminated samples.

Using a specific CAR design with a short linker (CAR.CD19 SL) enhances the ability of CAR T-cells to target and kill CD19+ leukemia cells, providing a potential safety advantage in preventing leukemic relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. Quintarelli, C., Guercio, M., Manni, S., et al.[2022]

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

CAR T cell therapy, particularly with the FDA-approved product tisagenlecleucel, has shown significant response rates in treating relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) in patients under 26 years old.

Despite its effectiveness, challenges such as high relapse rates, potential toxicities, and logistical issues in the therapy's production and administration remain significant barriers to its widespread application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience of CAR T cells for B cell acute lymphoblastic leukemia. Fabrizio, VA., Curran, KJ.[2022]

In a global study involving 75 pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), the CAR T-cell therapy tisagenlecleucel achieved an impressive overall remission rate of 81% within 3 months, with all responders showing no minimal residual disease.

While 73% of patients experienced serious adverse events, including cytokine release syndrome in 77% and neurologic events in 40%, these effects were mostly manageable and reversible, indicating that tisagenlecleucel can provide durable remission despite the risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. Maude, SL., Laetsch, TW., Buechner, J., et al.[2022]

Tisagenlecleucel, a CAR T-cell therapy for relapsed/refractory B-ALL, showed an 85% complete response rate in infused patients and a 12-month overall survival rate of 72%, indicating its efficacy in treating this condition.

Patients with a high disease burden before treatment had significantly worse outcomes and higher rates of severe side effects, highlighting the importance of disease status in predicting treatment success and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease Burden Affects Outcomes in Pediatric and Young Adult B-Cell Lymphoblastic Leukemia After Commercial Tisagenlecleucel: A Pediatric Real-World Chimeric Antigen Receptor Consortium Report. Schultz, LM., Baggott, C., Prabhu, S., et al.[2023]

Tisagenlecleucel is the first FDA-approved CD19-targeted CAR T cell therapy specifically for pediatric patients with pre-B-cell acute lymphoblastic leukemia (B-ALL), showing excellent responses in a multicenter phase II trial for those with highly refractory disease.

While CAR T cell therapy can lead to durable remissions in many patients, close monitoring for unique toxicities such as cytokine release syndrome and neurotoxicity is essential after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia. Pacenta, HL., Laetsch, TW., John, S.[2020]

Tisagenlecleucel and axicabtagene ciloleucel are groundbreaking CAR-T cell therapies that have shown high effectiveness in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and certain types of B-cell non-Hodgkin lymphomas.

This review highlights the challenges faced by physicians in administering these therapies and discusses future directions for research and treatment in the field of immune and cellular therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. Mohty, M., Gautier, J., Malard, F., et al.[2022]

Citations

1. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10294746/

Kymriah® (tisagenlecleucel) – An overview of the clinical ... This article presents a high-level overview of the clinical development journey of tisagenlecleucel, including its efficacy outcomes and safety considerations.

3. gilead.com gilead.com/news/news-details/2024/kite-to-highlight-industry-leading-car-t-cell-therapy-portfolio-at-ash-2024-including-positive-survival-outcomes-in-both-clinical-trials-and-the-real-world

Kite to Highlight Industry Leading CAR T Cell Therapy ... YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with large B- ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1914347

KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory ... KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma.

5. ashpublications.org ashpublications.org/bloodadvances/article/8/23/6114/518001/OUTREACH-phase-2-study-of-lisocabtagene-maraleucel

phase 2 study of lisocabtagene maraleucel as outpatient or ... CAR T-cell therapies using 4-1BB costimulatory domains have been associated with fewer CRS (42%-58%) and severe NEs (10%-12%) than those using ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9290945/

Efficacy and safety of CD19‐directed CAR‐T cell therapies in ... We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world.

7. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...