CAR-T Cell Therapy for Acute Lymphoblastic Leukemia

Overseen By Qing Liu-Michael, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: PeproMene Bio, Inc.

Must not be taking: Immunosuppressants, Systemic steroids

Disqualifiers: Auto-immune disease, Cardiovascular disability, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

24 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Will I have to stop taking my current medications?

The trial requires that you do not use immunosuppressant medications or systemic steroids before and during the study, except for low-dose steroid replacement. If you are on these medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the treatment BAFFR-CAR T cells for acute lymphoblastic leukemia?

Research shows that BAFFR-CAR T cells can effectively target and eliminate leukemia cells, even when other treatments fail due to antigen loss. In studies with mice, these cells successfully eradicated leukemia variants that had lost the CD19 marker, suggesting they could help prevent relapse in patients. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for treating acute lymphoblastic leukemia?

CAR-T cell therapy, including BAFF-R CAR T cells, has shown promise in treating acute lymphoblastic leukemia, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). Efforts are ongoing to improve the safety and reduce these side effects. ^{1 2 5 6 7}

What makes BAFFR-CAR T cell treatment unique for acute lymphoblastic leukemia?

BAFFR-CAR T cell treatment is unique because it targets the BAFF-R receptor, which is a B-cell survival receptor highly expressed in B-cell malignancies, offering a new approach for patients who may not respond to traditional CD19-targeting CAR T cell therapies. This treatment aims to improve therapeutic persistence and efficacy, addressing issues like antigen loss that can lead to disease relapse. ^{1 2 5 8 9}

Research Team

Ibrahim Aldoss, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults over 18 with B-cell Acute Lymphoblastic Leukemia that's come back or hasn't responded after at least two treatments. They must have BAFF-R on their cancer cells, be in decent physical shape (ECOG ≤ 2), and not pregnant or breastfeeding. People who've had certain other cancers, immune diseases, severe heart problems, recent transplants, or are HIV/HCV positive can't join.

Inclusion Criteria

My total bilirubin level is 2.0 mg/dL or less, or 3.0 if I have Gilbert's disease or liver-involved leukemia.

*If positive, Hepatitis C RNA quantitation must be performed and must be undetectable.

Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria

Any abnormal liver enzyme levels (as defined ≥ULN in ALT, AST, Bilirubin and Alkaline Phosphatase levels) at time of enrollment

I haven't needed strong medication for an autoimmune disease or graft-versus-host disease in the last 6 months.

I had a stem cell transplant within the last 100 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion prior to receiving BAFFR-CAR T cells

1 week

Treatment

Participants receive BAFFR-CAR T cells to target and kill BAFFR+ cancer cells

1 week

Follow-up

Participants are monitored for safety, effectiveness, and adverse events post-treatment

Up to 1 year

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 15 years

Treatment Details

Interventions

• BAFFR-CAR T cells

Trial Overview The trial is testing a new therapy using T cells engineered to target BAFFR on leukemia cells for patients whose leukemia has returned or resisted treatment. It's an early-phase study to see how safe it is and what effects it might have.

Participant Groups

Group I: BAFFR-CAR T cells Experimental Treatment 1 Intervention

B-cell activating factor receptor-Chimeric antigen receptor T cells

Who Is Running the Clinical Trial?

PeproMene Bio, Inc.

Lead Sponsor

Trials

2

Recruited

60+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

Findings from Research

The novel BAFF-R CAR T-cell therapy shows promise in treating B-cell malignancies, particularly in cases where traditional CD19-targeted therapies may fail due to antigen loss, with effective elimination of BAFF-R expressing tumors demonstrated in mouse models.

This therapy has been developed under strict manufacturing standards and has passed necessary FDA testing, paving the way for a Phase 1 clinical trial in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions. Dong, Z., Cheng, WA., Smith, DL., et al.[2020]

CAR-T cell therapy targeting CD19 has been FDA-approved for treating relapsed and refractory acute lymphoblastic leukemia (ALL) in children and young adults, showing promising efficacy.

Recent trials with CD22-directed CAR-T cells indicate they can also effectively target leukemia, providing a potential alternative to CD19 therapy, although challenges like toxicity management and relapse rates remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. Pehlivan, KC., Duncan, BB., Lee, DW.[2019]

The development of dual-targeting CAR T cells that target both CD19 and BAFF-R shows promise in overcoming treatment failures due to antigen loss in B-cell malignancies, specifically acute lymphoblastic leukemia (ALL).

In preclinical studies, these dual CAR T cells effectively eradicated both CD19- and BAFF-R-negative ALL variants in mice, demonstrating superior efficacy compared to single-target CAR T cells and suggesting potential for durable remissions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia. Wang, X., Dong, Z., Awuah, D., et al.[2023]

The development of BAFF-R CAR T cells shows promise in treating B cell malignancies, effectively targeting tumors even when CD19 expression is lost, which is a common issue with current therapies.

In preclinical models, BAFF-R CAR T cells successfully eradicated established tumors and demonstrated antitumor activity against relapsed cases of acute lymphoblastic leukemia (ALL) that had lost CD19 expression, suggesting a potential solution to tumor relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Qin, H., Dong, Z., Wang, X., et al.[2020]

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]

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]

An 11-year-old girl with relapsed acute B lymphoblastic leukemia (B-ALL) was treated with fourth generation CD19 CAR-T therapy, which was found to be effective and safe, resulting in a negative minimal residual disease after treatment.

Despite initial success and 10 months of disease-free survival, the patient ultimately relapsed due to increasing TEL-AML1 gene copies, highlighting the need for ongoing monitoring and potential further interventions in CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review]. Zuo, Y., Wang, J., Lu, A., 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]

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. Germany pubmed.ncbi.nlm.nih.gov

Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions. [2020]

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

CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. [2019]

3. England pubmed.ncbi.nlm.nih.gov

CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia. [2023]

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

CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. [2020]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Novel chimeric antigen receptor targets and constructs for acute lymphoblastic leukemia: Moving beyond CD19. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review]. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. [2022]

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

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