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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BAFFR-CAR T cells, a type of cell therapy, for individuals with B-cell Acute Lymphoblastic Leukemia (B-ALL) or B-cell lymphoblastic lymphoma, particularly those whose condition has recurred or not responded after at least two treatments. The primary goal is to determine the treatment's safety and its impact on the cancer. Suitable candidates for this trial have active B-ALL or B-cell lymphoblastic lymphoma and have not had success with other treatments. This trial specifically assesses the potential benefits of BAFFR-CAR T cells in managing the disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that BAFFR-CAR T cells are likely to be safe for humans?

Research has shown that BAFFR-CAR T cells are being tested for safety and effectiveness in treating B-cell Acute Lymphoblastic Leukemia. In a recent study, one patient with this leukemia type and three patients with non-Hodgkin lymphoma received BAFFR-CAR T cell treatment. The study aimed to determine the best dose and assess patient tolerance.

As an early phase study, the focus is on safety, so some side effects are expected. However, specific details about these side effects are not widely available yet. CAR T-cell therapies can cause side effects like fever or tiredness, but these can vary among individuals.

Since the study is still in its early stages, it continues to gather information to better understand safety. Those considering joining this trial should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy and radiation treatments for acute lymphoblastic leukemia, BAFFR-CAR T cells offer a groundbreaking approach by harnessing the body's own immune system. This treatment involves engineering a patient's T cells to express a chimeric antigen receptor (CAR) that specifically targets the B-cell activating factor receptor (BAFFR) on leukemia cells. This precise targeting could mean fewer side effects compared to conventional treatments, which often damage healthy cells. Researchers are excited about this therapy because it represents a personalized and potentially more effective treatment option for patients whose disease is resistant to existing therapies.

What evidence suggests that BAFFR-CAR T cells might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that a new treatment, CAR T cells targeting the BAFF-R protein on cancer cells, may effectively treat B-cell Acute Lymphoblastic Leukemia. This trial will specifically study BAFFR-CAR T cells, which is promising for cases where the usual target, CD19, is absent. Similar CAR T cell treatments have achieved success rates of up to 90% in B cell cancers. Early results suggest that these BAFF-R-targeting CAR T cells might succeed even when other treatments fail. While more research is needed, these findings offer hope for patients with relapsed or difficult-to-treat leukemia. ^{1 2 3 6 7}

Who Is on the Research Team?

Ibrahim Aldoss, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04690595

Study Details | NCT04690595 | BAFFR Targeting CAR-T ... This phase I trial evaluates the side effects and best dose of BAFFR-CAR T cells in treating patients with B-cell Acute Lymphoblastic Leukemia that has come ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8983465/

CD19/BAFF-R dual targeted CAR T cells for treatment of ... Clinical trials evaluating CD19-targeting chimeric antigen receptor (CAR) T cells have resulted in overall response rates of up to 90% in B cell ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6534

PMB-CT01 (BAFFR-CAR T cell) therapy to examine ... Results: As of Feb. 1st, 2024, 1 B-ALL and 3 NHL patients have completed treatment and post-treatment evaluations. Each received 50M BAFFR CAR T ...

4. probiologists.com probiologists.com/article/taking-baff-r-targeting-car-t-cells-on-the-road

Taking BAFF-R targeting CAR T-cells on the road CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Science Translational Medicine. 2019;11(511):eaaw9414.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7015136/

CAR T cells targeting BAFF-R can overcome CD19 antigen ... CAR T cells targeting CD19 provide promising options for treatment of B cell malignancies. However, tumor relapse from antigen loss can limit efficacy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7511472/

Antitumor efficacy of BAFF-R targeting CAR T cells ... We developed a prototype CAR T cell that efficiently and specifically eliminated BAFF-R expressing human B-cell tumors in several xenogeneic mouse models.

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04690595/

Clinical Trial: NCT04690595 - BAFFR(+) This phase I trial evaluates the side effects and best dose of BAFFR-CAR T cells in treating patients with B-cell Acute Lymphoblastic Leukemia ...