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

(24CT015 Trial)

Overseen By Cell Therapy Intake Team

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

Trial Summary

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.

What data supports the effectiveness of the treatment Allogeneic anti-CD7 CAR-T cells (BEAM-201) for T-Cell Lymphoblastic Leukemia/Lymphoma?

Research shows that CD7 CAR-T cells have shown promising results in treating T-cell acute lymphoblastic leukemia (T-ALL), with studies indicating they can effectively target and kill cancer cells. Additionally, CD7 is considered a strong target for this type of cancer, and similar treatments have demonstrated significant antitumor activity in both laboratory and animal studies. ^{1 2 3 4 5}

Is anti-CD7 CAR-T cell therapy safe for humans?

Research on anti-CD7 CAR-T cell therapy, including studies on donor-derived and genetically modified versions, shows promising safety results. In a Phase I clinical trial, no severe side effects like graft-versus-host disease or severe immune reactions were observed, although some patients experienced viral reactivations. ^{1 2 3 5 6}

What makes the treatment BEAM-201 unique for T-cell lymphoblastic leukemia/lymphoma?

BEAM-201 is unique because it uses allogeneic (donor-derived) anti-CD7 CAR-T cells, which are engineered to target the CD7 protein on cancerous T-cells. This approach is different from traditional treatments as it involves modifying donor T-cells to attack the cancer, potentially offering a new option for patients with relapsed or refractory T-cell lymphoblastic leukemia/lymphoma who have limited treatment choices. ^{1 2 3 4 5}

What is the purpose of this trial?

This will be a Phase 1, open-label study to evaluate the safety and efficacy of BEAM-201 in patients with R/R T-ALL or T-LLy. BEAM-201 is an allogeneic anti-CD7 CART therapy.

Research Team

Caroline Diorio, MD

Principal Investigator

Children's Hospital of Philadelphia

Stephan Grupp, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia. [2023]

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

Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial. [2021]

4. United States 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. [2023]

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

Engineering naturally occurring CD7- T cells for the immunotherapy of hematological malignancies. [2023]

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

Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study. [2023]