WU-CART-007 for Blood Cancers

Overseen by Geoffrey L. Uy

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: T-cell antibodies

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests WU-CART-007, a modified T-cell therapy, for patients with difficult-to-treat blood cancers. The therapy aims to specifically target and destroy cancer cells without causing harmful side effects. WU-CART-007 has shown potential in treating these types of cancers.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received systemic anticancer therapy or radiotherapy within 28 days before starting the trial, and certain other treatments like T-cell lytic antibodies within 8 weeks prior are also restricted.

What data supports the effectiveness of the treatment WU-CART-007 for blood cancers?

Research on WT1 peptide vaccines, which are part of the WU-CART-007 treatment, shows potential effectiveness in blood cancers like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Studies have shown that WT1 vaccination can lead to stable disease, reduction in cancer cells, and even complete remission in some patients, suggesting it may help in treating these conditions. ^{1 2 3 4 5}

What safety data is available for WU-CART-007 or similar CAR-T therapies in humans?

CAR-T therapies, like WU-CART-007, can cause side effects such as hematotoxicity (blood-related toxicity) and cytokine release syndrome (CRS), which can lead to symptoms like fever and low blood cell counts. Managing these side effects is important for patient safety. ^{6 7 8 9 10}

How is the WU-CART-007 treatment different from other treatments for blood cancers?

WU-CART-007 is a unique treatment for blood cancers because it uses modified T-cells to specifically target and attack cancer cells expressing the CD7 protein, which is common in T-cell malignancies. This approach is different from traditional therapies as it involves engineering the patient's own immune cells to fight the cancer, offering a new option for patients with relapsed or refractory T-cell cancers who have limited treatment choices. ^{3 11 12 13 14}

Research Team

Geoffrey L. Uy

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with certain blood cancers like T-cell lymphoma or acute myeloid leukemia (AML) that have come back or didn't respond to treatment can join. They must have CD7+ cancer cells, be in good physical condition, and not pregnant. They need proper organ function and no other effective treatments available.

Inclusion Criteria

My T-cell NHL is one of the allowed types.

Additional criteria include CD7 positive expression, age ≥ 18 years, ECOG Performance Status ≤ 2, adequate organ function, contraception requirement, ability to understand and sign informed consent, circulating blast count for AML patients, and no other effective standard of care therapy options

I am resistant or intolerant to treatments for my FLT3, IDH1, or IDH2 mutation.

Exclusion Criteria

Known hypersensitivity to study agents

Pregnant and/or breastfeeding

I am HIV positive.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Lymphodepletion

Patients receive preparative lymphodepletion in the week prior to WU-CART-007 infusion

1 week

Treatment

WU-CART-007 is infused 3 days following the last dose of chemotherapy at the assigned dose level

6 weeks

Multiple visits for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• WU-CART-007 (CAR T-cell Therapy)

Trial Overview The trial is testing WU-CART-007, a new type of CAR T-cell therapy for blood cancers expressing CD7. It's designed to avoid killing itself (fratricide-resistant) and prevent Graft-versus-Host-Disease by lacking certain cell receptors.

Participant Groups

Group I: Dose Expansion Cohort B: WU-CART-007 leukemia Experimental Treatment 1 Intervention

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the recommended phase II dose.

Group II: Dose Expansion Cohort A: WU-CART-007 T-NHL Experimental Treatment 1 Intervention

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the recommended phase II dose.

Group III: Dose Escalation Cohort B: WU-CART-007 leukemia Experimental Treatment 1 Intervention

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the assigned dose level.

Group IV: Dose Escalation Cohort A: WU-CART-007 T-NHL Experimental Treatment 1 Intervention

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the assigned dose level.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Wugen, Inc.

Industry Sponsor

Trials

8

Recruited

400+

Findings from Research

In a study of 58 patients with acute myeloid leukemia (AML), WT1 mRNA levels in peripheral blood did not differ based on initial treatment response, indicating that these levels may not be useful for predicting immediate treatment outcomes.

However, higher WT1 levels at the end of treatment were linked to a higher likelihood of disease relapse, suggesting that detectable WT1 transcripts after chemotherapy could serve as a prognostic marker for poor outcomes in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detectable Wilms' tumor-1 transcription at treatment completion is associated with poor prognosis of acute myeloid leukemia: a single institution's experience. Yamauchi, T., Negoro, E., Lee, S., et al.[2013]

The WT1-peptide vaccination was well tolerated in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), with a median of 11 vaccinations administered to 19 patients, showing promising safety.

The vaccination led to objective responses in AML patients, including stable disease in 10 patients and a complete remission in 1 patient, along with a significant increase in WT1-specific T cells, indicating potential clinical efficacy that merits further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Keilholz, U., Letsch, A., Busse, A., et al.[2022]

The WT1 peptide vaccine has shown promising clinical responses in patients with hematological malignancies, particularly myelodysplastic syndromes and acute myeloid leukemia, indicating its potential as an effective immunotherapy.

Recent studies suggest that WT1 peptide vaccination may lead to cures in patients with minimal residual disease after chemotherapy or stem cell transplantation, highlighting its significant therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy. Oka, Y., Tsuboi, A., Nakata, J., et al.[2018]

In a study of 125 acute myeloid leukemia (AML) patients, including 46 who were not in complete remission (non-CR), high levels of WT1 mRNA (≥5000 copies/μg RNA) before allogeneic hematopoietic cell transplantation (allo-HCT) were linked to a significantly increased risk of mortality, with a hazard ratio of 2.7.

The research suggests that pretransplant WT1 mRNA levels can serve as a strong prognostic indicator for survival after allo-HCT, indicating that higher levels may reflect greater tumor burden and could help identify non-CR patients who might benefit from the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Proportional Relationship Between Pretransplant WT1 mRNA Levels and Risk of Mortality After Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Not in Remission. Ido, K., Nakamae, M., Koh, H., et al.[2020]

In a study of 131 patients with myelodysplastic syndromes (MDS), higher levels of WT1 gene expression were found in patients with more severe forms of the disease, such as refractory anemia with excess blasts (RAEB) and secondary acute myeloid leukemia (s-AML), indicating its potential as a marker for disease progression.

The study demonstrated a strong correlation between WT1 expression levels and established prognostic factors, such as the International Prognostic Scoring System (IPSS) score, suggesting that WT1 could be a valuable tool for assessing risk and tracking the progression of MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant correlation between the degree of WT1 expression and the International Prognostic Scoring System Score in patients with myelodysplastic syndromes. Cilloni, D., Gottardi, E., Messa, F., et al.[2022]

In a study of 173 patients receiving CD19-targeted CAR T-cell therapy, 81% achieved neutrophil recovery and 75% achieved platelet recovery by day 28, although some experienced significant hematologic toxicity, including persistent neutropenia in 9% and thrombocytopenia in 14%.

The severity of cytokine release syndrome (CRS) was identified as an independent predictor of lower platelet counts, while lower pre-lymphodepletion platelet counts predicted decreased neutrophil and platelet recovery, suggesting that better management of CRS could enhance recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy. Juluri, KR., Wu, QV., Voutsinas, J., et al.[2022]

In a first-in-human study involving 10 older patients with acute myeloid leukemia (AML), adoptive transfer of NK cells derived from umbilical cord blood was well tolerated, showing no significant toxicity or graft-versus-host disease.

The treatment led to a notable reduction in minimal residual disease in some patients, with 2 out of 4 patients achieving MRD negativity for at least 6 months, suggesting that this NK cell therapy could be an effective new option for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients. Dolstra, H., Roeven, MWH., Spanholtz, J., et al.[2018]

The pharmacokinetics of SK&F 107647, a new hematoregulatory agent, were studied in rats, dogs, and humans, showing low plasma clearance and a distribution volume indicative of extracellular body water, suggesting a consistent behavior across species.

The study demonstrated that animal data (from rats and dogs) can effectively predict human pharmacokinetics for SK&F 107647, which is important for understanding its potential efficacy and safety in treating non-lymphoid solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interspecies pharmacokinetics of a novel hematoregulatory peptide (SK&F 107647) in rats, dogs, and oncologic patients. Brocks, DR., Freed, MI., Martin, DE., et al.[2019]

In a study of 71 patients with relapsed or refractory B-cell acute lymphoblastic leukemia or large B-cell lymphoma, early hematotoxicity occurred in 45.5% of B-ALL and 38.5% of LBCL patients following CAR-T therapy, highlighting the prevalence of this adverse effect.

The study developed a predictive model for early hematotoxicity based on peak levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), achieving high accuracy with positive predictive values of 87.7% and 85.0%, which can help identify high-risk patients for early intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risk factors and early predictive model of hematotoxicity after CD19 chimeric antigen receptor T cell therapy. Wang, Y., Song, Z., Geng, Y., et al.[2022]

In a phase 3b study involving 161 patients with polycythemia vera resistant or intolerant to hydroxyurea, ruxolitinib demonstrated a safety profile consistent with previous studies, with 37.9% of patients experiencing adverse events that required dose adjustments.

Ruxolitinib was effective, achieving hematocrit control in 45.3% of patients and significant spleen size reduction in 86.7%, indicating its potential as a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available. Foltz, L., Pica, GM., Zerazhi, H., et al.[2021]

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]

In a study of 147 patients with myelodysplastic syndromes (MDS), 82.3% showed positive expression of Wilms' tumor 1 (WT1), indicating its potential role as a biomarker for disease severity and classification.

Higher WT1 expression levels were linked to worse overall survival in patients who did not undergo transplantation, suggesting that WT1 could be an important factor in determining prognosis and treatment strategies for MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression of Wilms' Tumor 1 Gene in Bone Marrow of Patients with Myelodysplastic Syndrome and Its Clinical Significance]. Pan, DQ., Zhao, WS., Yin, CX., 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]

The study developed a novel CAR and secreted bi-specific T cell engager (sBite) targeting c-kit, a protein highly expressed in acute myeloid leukemia (AML), which is associated with poor prognosis and chemotherapy resistance.

Modified γδ T cells demonstrated the ability to kill c-kit+ AML cells in vitro and showed moderate survival benefits in mice with disseminated AML, although their effectiveness was limited by poor homing to the bone marrow, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia. Branella, GM., Lee, JY., Okalova, J., et al.[2023]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Detectable Wilms' tumor-1 transcription at treatment completion is associated with poor prognosis of acute myeloid leukemia: a single institution's experience. [2013]

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

A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy. [2018]

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

The Proportional Relationship Between Pretransplant WT1 mRNA Levels and Risk of Mortality After Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Not in Remission. [2020]

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

Significant correlation between the degree of WT1 expression and the International Prognostic Scoring System Score in patients with myelodysplastic syndromes. [2022]

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

Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy. [2022]

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

Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients. [2018]

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

Interspecies pharmacokinetics of a novel hematoregulatory peptide (SK&F 107647) in rats, dogs, and oncologic patients. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

The risk factors and early predictive model of hematotoxicity after CD19 chimeric antigen receptor T cell therapy. [2022]

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

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available. [2021]

11. England 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. [2022]

12. China pubmed.ncbi.nlm.nih.gov

[Expression of Wilms' Tumor 1 Gene in Bone Marrow of Patients with Myelodysplastic Syndrome and Its Clinical Significance]. [2022]

13. England 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. [2023]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia. [2023]