WU-CART-007 for T-Cell Leukemia

Recruiting at 8 trial locations

Overseen By Wugen Clinical Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Wugen, Inc.

Must not be taking: Steroids, Anti-neoplastic agents

Disqualifiers: HIV, Active hepatitis, CNS leukemia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called WU-CART-007, a type of cell therapy, for individuals with T-Cell Acute Lymphoblastic Leukemia (T-ALL) or Lymphoblastic Lymphoma (LBL) that has returned or resisted other treatments. The main goal is to determine if this treatment can completely eliminate the cancer. This trial may suit those diagnosed with T-ALL or LBL whose cancer has returned or not responded to other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that certain medications, like steroids or anti-cancer drugs, are not allowed. It's best to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that WU-CART-007 is likely to be safe for humans?

Research has shown that WU-CART-007 holds promise in safely treating T-cell leukemia. Studies have found it effective against leukemia with an acceptable safety level. While some side effects occurred, they were generally manageable.

In one study, 56% of patients experienced significant side effects, but these were expected and controllable. Overall, WU-CART-007 appears well-tolerated, making it a potential option for those fighting T-cell leukemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for T-cell leukemia, which often involve chemotherapy and stem cell transplants, WU-CART-007 is a CD7-directed chimeric antigen receptor (CAR) T-cell therapy. This innovative approach works by genetically modifying a patient's own T-cells to specifically target and attack cancer cells expressing the CD7 protein. Researchers are excited about WU-CART-007 because it offers a more precise attack on cancer cells, potentially reducing the collateral damage to healthy cells that is common with traditional treatments. This specificity could lead to more effective outcomes and fewer side effects for patients battling T-cell leukemia.

What evidence suggests that WU-CART-007 might be an effective treatment for T-Cell Leukemia?

Research has shown that WU-CART-007, the investigational treatment studied in this trial, yields promising results for treating T-Cell Acute Lymphoblastic Leukemia (T-ALL) and Lymphoblastic Lymphoma (LBL). This treatment uses specially modified immune cells to target and destroy cancer cells. Studies indicate that WU-CART-007 is effective against leukemia cells. In early trials, it benefited patients with relapsed or difficult-to-treat forms of the disease. Additionally, WU-CART-007 generally maintains a manageable safety profile, suggesting it could be a viable option for those unresponsive to standard treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Cherry Thomas, MD

Principal Investigator

Wugen, Inc.

Are You a Good Fit for This Trial?

This trial is for people with T-Cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma that didn't respond to initial treatment, relapsed within 24 months of diagnosis, failed re-induction therapy after recurrence, or have persistent disease after a stem cell transplant. Participants need normal liver and kidney function and adequate respiratory capacity.

Inclusion Criteria

My liver enzyme levels are not more than 5 times the normal limit.

My bilirubin levels are within the normal range, or slightly above if I have Gilbert's Syndrome.

My oxygen levels stay above 91% without extra oxygen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Therapy

Participants undergo lymphodepletion therapy prior to receiving the CAR-T cell infusion

1 week

Treatment

A single IV infusion of WU-CART-007 Cells on Day 1 after Lymphodepletion Therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• WU-CART-007

Trial Overview The study tests WU-CART-007, an experimental CAR-T cell therapy targeting CD7 in patients with relapsed/refractory T-cell leukemia/lymphoma. It aims to see if the treatment can achieve complete remission and eliminate minimal residual disease.

How Is the Trial Designed?

Group I: WU-CART-007 Experimental Treatment 1 Intervention

A CD7-directed chimeric antigen receptor (CAR) T-cell product. Lymphodepletion

Who Is Running the Clinical Trial?

Wugen, Inc.

Lead Sponsor

Trials

8

Recruited

400+

Published Research Related to This Trial

GC027, an allogeneic CAR-T therapy targeting the CD7 antigen, showed promising efficacy in two patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL), resulting in complete remission and no detectable minimal residual disease after treatment.

Both patients experienced grade 3 cytokine release syndrome, which was effectively managed with a ruxolitinib-based approach, indicating a potential strategy for managing side effects associated with CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management. Li, S., Wang, X., Yuan, Z., et al.[2022]

A novel immunotherapy targeting CD7 in T-cell acute lymphoblastic leukemia (T-ALL) was developed using CAR T cells, which showed over 99% CD7 expression in diagnostic samples, including aggressive subtypes.

To prevent fratricide (self-destruction of T cells), a new method called protein expression blocker (PEBL) was used, allowing CAR T cells to effectively target and kill CD7+ leukemic cells without harming themselves, demonstrating strong anti-leukemic activity in both lab and patient-derived models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Png, YT., Vinanica, N., Kamiya, T., et al.[2022]

Chimeric antigen receptor T-cell (CART) therapy has achieved impressive complete remission rates of 65% to 90% in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), marking a significant advancement in treatment.

The introduction of CART therapy has also brought new toxicity profiles and treatment challenges, highlighting the need for standardized toxicity grading systems and innovative management strategies to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies. Talleur, AC., Myers, R., Annesley, C., et al.[2022]

In a study involving 12 patients with relapsed and refractory T-cell acute lymphoblastic leukemia (T-ALL), the allogeneic CD7-targeted CAR-T therapy, GC027, led to rapid eradication of T-lymphoblasts, with 11 patients achieving complete response within one month after treatment.

GC027 showed a manageable toxicity profile and demonstrated superior clinical efficacy compared to standard chemotherapy, with one patient experiencing progression-free survival of over 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD7 targeted "off-the-shelf" CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies. Li, S., Wang, X., Liu, L., 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]

Allogeneic stem cell transplant is currently the only curative option for T-cell malignancies, but it carries significant risks and toxicities, highlighting the need for safer alternatives.

UCART7, a novel CAR-T therapy targeting the CD7 marker in T-cell malignancies, shows promise for treating relapsed T-cell acute lymphoblastic leukemia (T-ALL) and may offer a new option for patients with limited effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies. Cooper, ML., DiPersio, JF.[2020]

The novel NS7CAR T cells, derived from bulk T cells, effectively minimize fratricide by masking CD7 epitopes, showing similar or superior therapeutic properties compared to traditional CD7-targeted T cells in a phase 1 trial involving 20 patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL).

Nineteen out of 20 patients achieved minimal residual disease negative complete remission by day 28, with a median follow-up of 142.5 days showing no relapses in patients who received a stem cell transplant, indicating that NS7CAR-T therapy is both safe and highly effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial. Lu, P., Liu, Y., Yang, J., et al.[2022]

A case study of an 11-year-old boy with relapsed/refractory ETP-ALL/LBL showed that CD7-targeted CAR T-cell therapy effectively achieved remission from both hematological and extramedullary disease after traditional therapies failed.

The treatment was associated with reversible side effects, including grade 3 cytokine release syndrome, indicating that while CD7-CART therapy is potent, it also requires careful monitoring for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical CD7 CAR T-cells induced remission in a patient with TP53 mutated relapsed and refractory early T-cell precursor lymphoblastic leukemia/lymphoma. Dai, HP., Cui, W., Cui, QY., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/146/10/1163/537566/Phase-1-2-trial-of-anti-CD7-allogeneic-WU-CART-007

Phase 1/2 trial of anti-CD7 allogeneic WU-CART-007 for ... WU-CART-007, an allogeneic anti-CD7 chimeric antigen receptor T cell, established a manageable safety profile at the RP2D of 900 × 106 cells ...

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

Anti-CD7 allogeneic WU-CART-007 in patients with relapsed ... Current standard chemotherapy regimens lead to poor outcome with 6 months median overall survival in responders (1).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06514794

NCT06514794 | A Phase 2 Study of WU-CART-007, an ... A Phase 2 Study of WU-CART-007, an Anti-CD7 Allogeneic CAR-T Cell Therapy in T-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (T-RRex).

4. wugen.com wugen.com/phase-2-findings-show-wugens-investigational-allogeneic-car-t-wu-cart-007-was-highly-effective-and-surpassed-standard-of-care-in-treating-hard-to-treat-t-all-lbl-data-presented-today-at-eu/

Phase 2 Findings Show Wugen's Investigational ... Researchers shared findings including a clinically manageable safety profile and anti-leukemic activity with WU-CART-007 in patients with R/R T-ALL/LBL.

5. ashpublications.org ashpublications.org/blood/article/146/10/1145/547031/CART-007-a-license-to-kill

CART-007: a license to kill | American Society of Hematology Collectively, data from these clinical trials show potent antileukemic efficacy with an acceptable safety profile, suggesting that CAR T-cell ...

6. hematologyadvisor.com hematologyadvisor.com/reports/leukemia-wu-cart-007-antileukemic-activity-safety-profile-treatment-risk/

WU-CART-007 Showed Antileukemic Activity, Acceptable ... Treatment with WU-CART-007 was associated with antileukemic activity and an acceptable safety profile in a recent phase 2 study.

7. wugen.com wugen.com/wp-content/uploads/2023/12/2023-ASH-WUCART7_FINAL.pdf

WUCART7 1001 Phase 1/2 Dose-Escalation/ ... - Wugen WU-CART-007 demonstrated manageable safety. Treatment-related adverse events of ≥ Gr 3 were observed in 14/25 (56%) patients.