Multi Tumor-Associated Antigen-Specific T Lymphocytes to Treat Patients With High Risk Solid Tumors

NCT05238792 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ATTACK
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I dose-escalation study to evaluate the safety of partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T cell (TAA-T) therapy for patients with high-risk solid tumors due to the presence of refractory, relapsed and/or minimal residual detectable disease following conventional therapy. Conventional therapy may include chemotherapy, surgery, radiation, autologous stem cell transplant, or targeted therapy.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• The rate of toxicities after TAA-T infusion

  * Incidence of grades 3 to 5 infusion-related adverse event occurring within 45 days of the first TAA-T infusion. * Incidence of grades 4 to 5 non-hematologic adverse event related to TAA-T product occurring within 45 days of the first TAA-T infusion and that are not due to the patient's underlying malignancy or pre-existing co-morbidities. * Incidence of grades 3 to 4 acute GVHD occurring within 45 days of the first TAA-T infusion. * Incidence of unexpected toxicities of any grade attributed to the infusion of TAA-T occurring within 45 days of the first TAA-T dose.

  45 days

Secondary Outcomes (1)

• Anti-tumor activity based on tumor response

  1 year

Study Arms (2)

Arm A for patients age ≥18 years and <70 years

EXPERIMENTAL

Arm A will enroll patients age ≥18 years and \<70 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.

Biological: Tumor-associated antigen-specific T cell (TAA-T)

Arm B for patients age ≥6 years and <18 years

EXPERIMENTAL

Arm B will enroll patients age ≥6 years and \<18 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.

Biological: Tumor-associated antigen-specific T cell (TAA-T)

Interventions

Tumor-associated antigen-specific T cell (TAA-T) BIOLOGICAL

Patients will receive an infusion of partially HLA-matched TAA-T any time \>1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy \>2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels: BSA \<1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells

Arm A for patients age ≥18 years and <70 years; Arm B for patients age ≥6 years and <18 years

Eligibility Criteria

• Age: 6 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Central Study Contacts

Amy Hont, MD

CONTACT

202-476-3887; ahoughte@childrensnational.org

Fahmida Hoq, MBBS

CONTACT

202-476-3634; fhoq@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oncologist

Study Record Dates

• First Submitted: February 3, 2022
• First Posted: February 14, 2022
• Study Start: November 17, 2021
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)