CAR-T Cell Therapy for B-Cell Leukemia

(TRICAR-ALL Trial)

Recruiting at 1 trial location

Overseen By Nabil Ahmed, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids, TKIs, Hydroxyurea, others

Disqualifiers: Active malignancy, Severe infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 day

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Acute Lymphoblastic Leukemia (ALL) that has not responded to other treatments. The study uses CAR-T cell therapy, which modifies the body's T cells (a type of white blood cell that fights infections) to better target and kill cancer cells. Specifically, the trial enhances these T cells by adding proteins to make them stronger and last longer in the body, increasing their ability to fight leukemia. This trial specifically uses TriCAR T-cells, a form of CAR-T cell therapy. Individuals with B-ALL that has returned or persisted after treatment and have specific markers on their cancer cells (CD19, CD20, or CD22) may be suitable for this study. 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 innovative therapy.

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

Yes, you will need to stop certain medications before participating in the trial. Chemotherapy and biologic therapy must be stopped at least 7 days before collection, systemic corticosteroids 7 days prior, Tyrosine Kinase Inhibitors 3 days prior, and Hydroxyurea 1 day prior. Other specific medications have different requirements, so it's important to discuss your current medications with the trial team.

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

Research has shown that CAR-T cell therapies targeting CD19 can effectively treat B cell cancers like leukemia. Studies have found that these therapies can lead to long-lasting remissions, keeping the cancer at bay for extended periods. However, some side effects require attention. Cytokine Release Syndrome (CRS) occurred in about 81.8% of patients. CRS arises when the immune system becomes overly active, often causing symptoms like fever and tiredness.

On a positive note, many patients did not experience long-term negative effects, indicating that while immediate side effects may occur, they might not persist. These treatments remain under study and have not yet received FDA approval for general use. Nonetheless, the research so far is promising for their safety and effectiveness in treating blood cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell leukemia, which typically involve chemotherapy and targeted therapies, TriCAR T-cells offer a novel approach by using the body's own immune system to fight cancer. This treatment is unique because it involves reprogramming a patient's T-cells to specifically target and destroy cancerous B-cells. Researchers are excited about TriCAR T-cells because they have the potential to be more precise and effective, potentially leading to fewer side effects and longer-lasting remissions compared to traditional therapies. By harnessing the power of the immune system, TriCAR T-cells could revolutionize the way we treat B-cell leukemia.

What evidence suggests that TriCAR T-cells might be an effective treatment for B-cell leukemia?

Research has shown that CAR-T cell therapy, particularly when targeting the CD19 protein, holds promise for treating certain blood cancers like Acute Lymphoblastic Leukemia (ALL). Studies have found that CD19 CAR-T cells can lead to complete remission in about 80-90% of patients whose B-ALL has returned or resisted other treatments. In this trial, participants will receive the experimental treatment of Autologous TRICAR-ALL T-Cells following lymphodepletion chemotherapy. Proteins like 4-1BB enhance these T cells' growth and longevity, boosting their ability to combat leukemia. Although researchers are still studying this therapy, early results offer hope for those with hard-to-treat leukemia. ^{1 3 6 7 8}

Who Is on the Research Team?

Meenakshi Hegde, MD

Principal Investigator

Baylor College of Medicine

Bahey Salem, MD

Principal Investigator

Baylor College of Medicine

Nabil Ahmed, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for young people aged 12 months to 21 years with B cell Acute Lymphoblastic Leukemia that's resistant or has returned. They must weigh at least 10 kg, have certain levels of liver and kidney function, a good heart function score, and be expected to live more than 8 weeks. Those who can get pregnant must agree to use effective birth control during the study.

Inclusion Criteria

I am over 18 and can make my own health decisions or have a guardian who can.

I have stopped all cancer treatments and recovered from their major side effects.

I am between 12 and 21 years old and eligible for the TRICAR-ALL T cell infusion.

Exclusion Criteria

Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol

I do not have any cancer other than the one being studied.

I have a brain condition that needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Chemotherapy

Participants receive lymphodepletion chemotherapy with Cyclophosphamide for 2 days and Fludarabine for 4 days

6 days

Daily visits during chemotherapy

Treatment

Participants receive an infusion of TRICAR-ALL T-cells and are monitored for up to 3 hours post-infusion

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and effectiveness with regular visits and tests

4 weeks

Visits on days 1, 4, 7, 10, 14, 28 post-infusion

Extended Follow-up

Participants continue to be monitored for long-term safety and effectiveness

15 years

Visits at 3, 6, 12 months, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Lymphodepletion chemotherapy
• TriCAR T-cells

Trial Overview The trial tests 'TRICAR-ALL' T-cells combined with lymphodepletion chemotherapy in patients with leukemia. These special T-cells are engineered in the lab to target cancer cells more effectively by using a modified antibody that sticks to three specific proteins on leukemia cells.

How Is the Trial Designed?

Group I: Autologous TRICAR-ALL T-Cells and lymphodepletion chemotherapy Experimental Treatment 1 Intervention

Three dose levels will be evaluated. The TRICAR-ALL T-cells will be administered after lymphodepletion chemotherapy with Cyclophosphamide and fludarabine.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Texas Children's Cancer Center

Collaborator

Trials

8

Recruited

220+

Published Research Related to This Trial

In a study of 43 patients with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) who relapsed after an allotransplant, 79% achieved complete remission after receiving allogeneic anti-CD19 CAR-T cells, indicating high efficacy of this treatment.

While the therapy was effective, it was associated with a high incidence of cytokine release syndrome (CRS) in 88% of patients, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Zhang, C., Wang, XQ., Zhang, RL., et al.[2021]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

Autologous anti-CD19 CAR T-cell therapy has been approved by the FDA as an effective treatment for B-cell acute lymphoblastic leukemia (B-ALL), showcasing its potential in improving patient outcomes.

The review discusses the evolving role of allogeneic stem cell transplants alongside CAR T-cell therapy and highlights future innovations in CAR technology that may enhance treatment options for B-ALL, including alternative targets and off-the-shelf solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy for adult B-cell acute lymphoblastic leukemia: state-of-the-(C)ART and the road ahead. Pasvolsky, O., Kebriaei, P., Shah, BD., et al.[2023]

CAR T cell therapy has shown effectiveness in treating various hematological malignancies, including B lymphoblastic leukemia and lymphoma, with advancements in CD19, BCMA, and CD7 CAR-T cells.

Research is ongoing to improve CAR T cell therapies by developing multi-target and universal CAR-T cells, as well as iPSC-derived CAR cells, aiming for enhanced efficacy and reduced side effects in treating myeloid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress on CAR-T cell therapy for hematological malignancies. Hu, K., Huang, Y., Hu, Y., et al.[2022]

CAR-T cell therapy can be safely administered to remission patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), showing promising results without severe side effects, such as neurotoxicity.

In this study involving two patients, CAR-T therapy combined with maintenance chemotherapy led to over three and a half years of event-free survival, suggesting it may be an effective alternative to transplantation for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T therapy as a consolidation in remission B-ALL patients with poor prognosis. Yin, Z., Lin, Y., Liu, D., et al.[2022]

CAR T cell therapy, specifically targeting the CD19 antigen, has shown high response rates in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), indicating its potential as a new treatment option.

Despite its effectiveness, CAR T cell therapy is associated with severe toxicities like cytokine release syndrome and neurotoxicity, which pose challenges for its widespread use and highlight the need for ongoing improvements in the technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. Luskin, MR., DeAngelo, DJ.[2018]

CAR-T cell therapy has shown remarkable efficacy in treating B cell malignancies, including leukemia, lymphoma, and multiple myeloma, with high response rates, but it comes with significant safety concerns.

The most serious side effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require supportive care and specific treatments like tocilizumab and steroids to manage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. Chohan, KL., Siegler, EL., Kenderian, SS.[2023]

In a phase-1/2 trial involving 13 adult patients with refractory acute lymphoblastic leukemia, third-generation CAR T cells (CARTs) demonstrated promising efficacy, with 80% of evaluable patients achieving complete remission, including 50% with no detectable residual disease.

The treatment was associated with remarkably low toxicity, as none of the patients experienced severe side effects like neurotoxicity or high-grade cytokine release syndrome, indicating a favorable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. Schubert, ML., Schmitt, A., Hückelhoven-Krauss, A., et al.[2023]

Engineered T cells expressing a chimeric antigen receptor (3CAR) targeting CD3 can be successfully created by disrupting the TCRαβ/CD3 complex, allowing for the generation of viable T cells that do not self-destruct.

These 3CAR T cells demonstrated effective cytotoxicity against both healthy primary T cells and childhood T cell acute lymphoblastic leukemia (T-ALL), showing promise for treating T cell malignancies and potentially aiding in leukemic remission before stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCRαβ/CD3 disruption enables CD3-specific antileukemic T cell immunotherapy. Rasaiyaah, J., Georgiadis, C., Preece, R., et al.[2022]

CAR T-cell therapy has shown remarkable success in treating B-cell acute lymphoblastic leukemia by targeting the CD19 marker, which is present on most B-cell tumors.

The therapy is being explored for other B-cell malignancies, including chronic lymphocytic leukemia and various types of lymphoma, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Pegram, HJ., Smith, EL., Rafiq, S., et al.[2018]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05010564

NCT05010564 | Trivalent CAR-T Cell in Acute B-Lineage ... The TRICAR-ALL T-cells were made in the laboratory by stimulating the patient's blood with growth factors to make the T cells grow. To get the CD19/CD20/CD22 ...

2. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy The data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5877/527643/Long-Term-Outcomes-and-Adverse-Events-of-CAR-T-19

Long-Term Outcomes and Adverse Events of CAR T-19 Cell ... Anti-CD19 CAR T-cell therapy showed the highest efficacy with an event rate of 74.75% (95% CI: 61% to 80%, I² = 89.84%). Combination therapies ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10786140/

CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia CD19 CAR-T cells induce a high rate (80–90%) of complete remissions in both pediatric and adult R/R B-ALL patients. However, despite this impressive rate of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723014203

Clinical Variables Associated with Improved Outcomes for ... Multiple clinical trials and retrospective real-world analyses have shown event-free survival (EFS) rates of 50% to 60% at 1 year after CAR T cell infusion [2,9 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10100620/

Long-term outcomes following CAR T cell therapy The data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e19530

Safety and efficacy of allogeneic CAR-T cells in B- ... Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in < ...

8. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06608-x

Efficacy and safety of third-generation CD19-CAR T cells ... The overall response rate in this study is comparable at 71% (15/21), and was similar among patients with B-ALL and B-NHL. The estimated 12- ...