Using T cells to treat high-risk solid tumors

Phase I Research Study Utilizing Allogeneic Multi Tumor-Associated Antigen-Specific T Lymphocytes to Advance the Care of Patients With High-Risk Solid Tumors

This study is testing a new type of immune therapy using T cells to see if it can help people with high-risk solid tumors that haven't improved with standard treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 6 Years to 70 Years
• Sex: All
• Sponsor: Children's National Research Institute (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Washington D.C., District of Columbia)
• Trial ID: NCT05238792 on ClinicalTrials.gov

What this trial studies

This phase I dose-escalation trial evaluates the safety of partially HLA-matched multi tumor-associated antigen-specific T cell (TAA-T) therapy for patients with high-risk solid tumors that have not responded to conventional treatments. The study includes two arms based on age, with patients receiving TAA-T therapy after a lymphodepleting chemotherapy regimen. The trial aims to assess both the safety and anti-tumor activity of the TAA-T product across different dose levels. Participants will be monitored for their response to the treatment following their previous therapies.

Who should consider this trial

Good fit: Ideal candidates include patients aged 6 to 70 years with high-risk solid tumors expressing specific targeted antigens and who have refractory or relapsed disease.

Not a fit: Patients with solid tumors that do not express the targeted antigens or those who are not within the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with high-risk solid tumors that are resistant to standard therapies.

How similar studies have performed: Other studies using T cell therapies for solid tumors have shown promise, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

PARTICIPANT INCLUSION CRITERIA

RECIPIENT SCREENING INCLUSION CRITERIA

* Diagnosis of high-risk solid tumors known to express at least 2 targeted antigens by either histology or historical reference: Ewing sarcoma, Wilms tumor, neuroblastoma, rhabdomyosarcoma, soft tissue sarcoma, and osteosarcoma.
* HLA type and match through at least one allele with antigen-specific activity.
* Refractory disease, residual detectable disease following conventional therapy or relapsed disease.
* Arm A: age ≥18 years and \<70 years
* Arm B: age ≥6 years to \<18 years
* Patient or parent/guardian capable of providing informed consent.

RECIPIENT INCLUSION CRITERIA FOR INITIAL TAA-T ADMINISTRATION AND FOR SUBSEQUENT INFUSION

* No systemic steroid exposure within 1 week of TAA-T infusion.
* Karnofsky/Lansky score of ≥50% (see Appendix 4).
* Left ventricular ejection fraction (LVEF) \>50% or left ventricular systolic dysfunction (LVSD) \>27% if history of total body irradiation (TBI) (may be performed within the last 6 months).
* Hemoglobin \>7.0 g/dL (level can be achieved with transfusion).
* Bilirubin ≤2.5 mg/dL.
* Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤5 x the upper limit of normal for age.
* Serum creatinine \<1.0 mg/dL or 2x the upper limit of normal for age (whichever is higher).
* Pulse oximetry of \>90% on room air.
* Negative pregnancy test in female patient of childbearing age.
* Agree to use contraceptive measures during study protocol participation (when age appropriate).
* Patients receiving lymphodepleting chemotherapy must have:

  * Absolute neutrophil count (ANC) \>1000 /ul.
  * Platelet count \>75,000 /ul.

Exclusion Criteria:

PARTICIPANT EXCLUSION CRITERIA RECIPIENT SCREENING EXCLUSION CRITERIA

* Patients with known human immunodeficiency virus (HIV) infection.
* Pregnant or lactating females.
* Patients who have undergone previous allogeneic stem cell transplant.
* Patients who have undergone previous autologous stem cell transplant within the past 60 days.

RECIPIENT EXCLUSION CRITERIA FOR INITIAL AND SUBSEQUENT TAA-T INFUSION

* Patients with uncontrolled infections. Uncontrolled infections are defined as bacterial, fungal, or viral infections with either clinical signs of worsening despite standard therapy. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.

  * For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to TAA-T infusion.
  * For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to TAA-T infusion.
* Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days prior to TAA-T infusion.
* For patients receiving lymphodepleting chemotherapy: exposure to chemotherapy or immunomodulatory medications within the last 2 weeks prior to treatment.
* Pregnant or lactating females.

Where this trial is running

Washington D.C., District of Columbia

• Children's National Hospital — Washington D.C., District of Columbia, United States (RECRUITING)

Study contacts

• Study coordinator: Amy Hont, MD

Conditions: Solid Tumor