Anti-CD7 CAR-T Cells for T-Cell Lymphoblastic Leukemia/Lymphoma

(24CT015 Trial)

Overseen By Melissa S Varghese, M.S.

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stephan Grupp MD PhD

Must not be taking: Corticosteroids, CD7 therapy

Disqualifiers: CNS disease, Organ dysfunction, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BEAM-201, which uses specially modified immune cells (anti-CD7 CAR-T cells) to target and fight T-cell leukemia and lymphoma. The main goal is to determine if this treatment is safe and effective for individuals whose disease has returned or who haven't responded to other treatments. For those with difficult-to-treat or relapsed T-cell leukemia or lymphoma, this trial might be suitable. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use systemic corticosteroids for conditions unrelated to T-ALL/T-LLy, except for adrenal insufficiency treatment.

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

In the BEAM-201 study, researchers tested a new treatment for safety in patients with certain types of blood cancer that had returned or didn't respond to other treatments. Most patients tolerated the treatment well, with no serious side effects. Some experienced mild to moderate side effects, which is common with such treatments.

This treatment remains in the early stages of testing, and researchers continue to study its safety. However, the initial results are promising, suggesting it might be a safe option for trial participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for T-cell lymphoblastic leukemia/lymphoma, which often include chemotherapy and stem cell transplants, the anti-CD7 CAR-T cells (BEAM-201) offer a novel approach. This treatment is unique because it uses a patient's own immune cells, genetically engineered to target the CD7 protein on cancerous T-cells, providing a more precise attack on the cancer. Researchers are excited about BEAM-201 because it represents a targeted therapy that could potentially offer higher efficacy and fewer side effects compared to traditional treatments. Additionally, the ability to expand the dose once safety is established gives hope for optimizing its therapeutic potential.

What evidence suggests that this treatment might be an effective treatment for T-Cell Lymphoblastic Leukemia/Lymphoma?

Research has shown that BEAM-201, a type of cell therapy, offers promising early results for treating certain blood cancers, specifically T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL), when they return or resist other treatments. One study found that 3 out of 4 adult patients with T-ALL who received this treatment responded positively, with a reduction in cancer cells in their blood. In this trial, participants will receive BEAM-201, designed to target and attack cancer cells with a specific marker called CD7 on their surface. Early results suggest that this method can help control the disease by using the body's own modified immune cells. ^{1 2 3 4 6}

Who Is on the Research Team?

Caroline Diorio, MD

Principal Investigator

Children's Hospital of Philadelphia

Stephan Grupp, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for people with certain types of blood cancer, including T-Cell Lymphoblastic Lymphoma and Acute Lymphoblastic Leukemia, who have tried other treatments that didn't work. Specific eligibility details are not provided but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

Negative urine or serum pregnancy test at screening for patients of childbearing potential

Agreement to use effective contraception for sexually active patients of reproductive potential

My brain-related disease responded to treatment.

Exclusion Criteria

Positive serology for HIV, HTLV, Hepatitis B, or Hepatitis C

Conditions making the patient ineligible for HSCT as determined by the investigator

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

The dose escalation portion of the trial will use a standard '3+3' design to establish the recommended maximum tolerated dose of BEAM-201 cells.

Varies

Dose Expansion

If at least one dose level of the dose escalation phase is determined to be safe, the dose expansion phase of the trial will be opened to enrollment.

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic anti-CD7 CAR-T cells (BEAM-201)

Trial Overview The study is testing BEAM-201, a new type of cell therapy targeting CD7 on cancer cells. It's an early-phase trial to see if this treatment is safe and how well it works in patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoma.

How Is the Trial Designed?

Group I: Dose Expansion Arm Experimental Treatment 1 Intervention

If at least one dose level of the dose escalation phase is determined to be safe, the dose expansion phase of the trial will be opened to enrollment.

Group II: Dose Escalation Arm Experimental Treatment 1 Intervention

The dose escalation portion of the trial will use a standard "3+3" design to establish the recommended maximum tolerated dose of BEAM-201 cells. Three dose escalations of BEAM-201 are planned for the dose escalation phase, with one dose de-escalation level if needed.

Who Is Running the Clinical Trial?

Stephan Grupp MD PhD

Lead Sponsor

Trials

5

Recruited

370+

Beam Therapeutics Inc.

Industry Sponsor

Trials

5

Recruited

1,200+

Published Research Related to This Trial

In a phase I clinical trial involving 7 patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma, CD7 CAR-T therapy achieved a remarkable 100% complete remission rate by day 28, demonstrating its strong efficacy.

However, the treatment was associated with significant safety concerns, including severe infections leading to the deaths of 2 patients, highlighting the need for careful monitoring of immune reconstitution and potential complications post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy. Chen, W., Shi, H., Liu, Z., et al.[2023]

CD7-CAR T cells, which are modified to avoid fratricide by using naturally occurring CD7- T cells, showed strong antitumor activity against T-cell acute lymphoblastic leukemia (T-ALL) in both laboratory and mouse models.

In a comparison of CD19-CAR T cells, those derived from CD7- T cells demonstrated enhanced antitumor effects, and a higher presence of CD7-low expressing T cells was associated with better patient responses in a clinical study, suggesting a promising avenue for immunotherapy in hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering naturally occurring CD7- T cells for the immunotherapy of hematological malignancies. Freiwan, A., Zoine, JT., Crawford, JC., et al.[2023]

In a clinical trial involving patients with relapsed and refractory T-lymphoblastic leukemia/lymphoma (T-ALL/LBL), autologous CD7-CAR T cells achieved a high complete remission rate of 87.5%, indicating strong efficacy in treating this aggressive cancer.

The treatment was well-tolerated, with most patients experiencing only mild cytokine release syndrome and no severe toxicities, suggesting a favorable safety profile for this innovative immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma. Zhang, M., Chen, D., Fu, X., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124075967

BEAM-201 for the Treatment of Relapsed and/or Refractory ... BEAM-201 is an investigational allogeneic, multiplex base-edited anti-CD7 CAR-T-cell therapy designed to address these limitations.

2. beamtx.com beamtx.com/wp-content/uploads/2024/12/BEAM-201-for-the-Treatment-of-Relapsed-andor-Refractory-RR-T-Cell-Acute-Lymphoblastic-Leukemia.pdf

BEAM-201 for the Treatment of Relapsed and/or Refractory ... BEAM-201 for the Treatment of Relapsed and/or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LL): Initial Data ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06934382

Study Details | NCT06934382 | Anti-CD7 CAR-T Cells in ... BEAM-201 is an allogeneic anti-CD7 CAR T cell product that has shown promising early evidence of efficacy, with 3 out of 4 adult T-ALL patients infused had a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11326362/

Anti-CD7 allogeneic WU-CART-007 in patients with relapsed ... A reduction in CD7pos T-cell acute lymphoblastic leukemia and increase in WU-CART-007 with expression of cytotoxic markers was observed in peripheral blood, ...

5. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4838/533281/BEAM-201-for-the-Treatment-of-Relapsed-and-or

BEAM-201 for the Treatment of Relapsed and/or Refractory (R ... Initial data from the Phase (Ph) 1/2 dose-exploration, dose-expansion, safety, and efficacy study of multiplex base-edited allogeneic anti-CD7 CAR-T-cells.

6. stanfordhealthcare.org stanfordhealthcare.org/trials/a/NCT05885464.html

A Study Evaluating the Safety and Efficacy of BEAM-201 in ... This is a Phase 1/2, multicenter, open-label study to evaluate the safety and efficacy of BEAM-201 in patients with relapsed/refractory T-ALL or T-LL. This ...