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

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for patients with a type of blood cancer called Acute Lymphoblastic Leukemia (ALL) that hasn't responded to other treatments. The treatment uses the patient's own T cells, which are modified in the lab to better fight cancer. These enhanced T cells are then reintroduced into the patient's body to target and kill cancer cells more effectively. This therapy has shown promise in treating relapsed or refractory acute lymphoblastic leukemia (ALL).

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.

What data supports the effectiveness of the treatment CAR-T Cell Therapy for B-Cell Leukemia?

Research shows that CAR-T cell therapy targeting CD19 has led to complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia, which is significantly higher than the 30% response rate expected with traditional chemotherapy. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapy has shown significant safety concerns, including severe toxicities like cytokine release syndrome (CRS) and neurotoxicity, which can be life-threatening. While it has been effective in treating B-cell leukemia, these side effects are a major challenge in its broader use. ^{6 7 8 9 10}

What makes TriCAR T-cells treatment unique for B-cell leukemia?

TriCAR T-cells are a type of CAR-T cell therapy that involves genetically modifying a patient's own T-cells to better recognize and attack cancer cells. This treatment is unique because it targets specific markers on B-cell leukemia cells, potentially leading to higher remission rates compared to traditional chemotherapy. ^{1 3 11 12 13}

Research Team

Bahey Salem, MD

Principal Investigator

Baylor College of Medicine

Meenajshi Hegde, MD

Principal Investigator

Baylor College of Medicine

Nabil Ahmed, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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-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]

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]

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, 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]

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 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 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]

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]

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 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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

TCRαβ/CD3 disruption enables CD3-specific antileukemic T cell immunotherapy. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. [2023]

9. United States 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. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia. [2023]

11. England 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? [2018]

12. China pubmed.ncbi.nlm.nih.gov

Progress on CAR-T cell therapy for hematological malignancies. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

CAR-T therapy as a consolidation in remission B-ALL patients with poor prognosis. [2022]