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: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label 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 following lymphodepleting conditioning with or without local tumor ablation for pediatric and adult patients with high-risk solid tumors due to the presence of refractory, relapsed and/or minimal residual detectable disease following conventional therapy (e.g., chemotherapy, surgery, radiation, autologous stem cell transplant, or targeted therapy).

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• To determine the safety of administering partially HLA-matched TAA-T cells

  Safety will be evaluated by the incidence of dose-limiting toxicities (DLTs).

  45 days

Secondary Outcomes (1)

• Treatment feasibility and impact of TAA-T infusion

  Within 12 months of TAA-T infusion

Study Arms (1)

TAA-T Infusion

EXPERIMENTAL

Treatment with partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T cell (TAA-T) therapy following lymphodepleting conditioning with or without local tumor ablation.

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

Interventions

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

Patients will receive cells due to the presence of refractory disease, or high risk for disease relapse and/or minimal residual detectable disease following conventional therapy. The treatment schedule is as follows: Patients will receive an infusion of partially HLA-matched TAA-T any time \>1 week after completing most recent course of conventional (noninvestigational) therapy for their disease. For patients enrolled to DL2 or DL3, they will receive protocol-described lymphodepletion (LD) chemotherapy (fludarabine and cyclophosphamide) \>2 weeks from most recent course of conventional therapy and post nadir and recovery from the prior therapy. Patients will be enrolled to one of the following TAA-T dose levels: BSA \<1.20 Dose Level 2 (+/- ablation + low dose TAA-T cells) 2x10\^7 Dose Level 3 (+/- ablation + high dose TAA-T cells) 4x10\^7 BSA\>=1.20 Dose Level 2 (+/- ablation + low dose TAA-T cells) 4x10\^7 Dose Level 3 (+/- ablation + high dose TAA-T cells) 8x10\^7

TAA-T Infusion

Eligibility Criteria

• Age: 1 Year - 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.
• Following conventional therapy: refractory disease, residual detectable disease, or relapsed disease.
• Age \>= 1 year and \<70 years
• Patient or parent/guardian capable of providing informed consent.
• No systemic corticosteroid exposure within 1 week of initiating protocol treatment.
• Karnofsky/Lansky score of ≥50%.
• For participant with history of total body irradiation (TBI), radiation to thorax, or treatment with cardiotoxic chemotherapy (anthracycline or equivalent): Left ventricular ejection fraction (LVEF) \>50% OR left ventricular fractional shortening (FS) \>27% (may be performed within the last 12 months, and after completion of such treatment/s)
• Hemoglobin \>7.0 g/dL (level can be achieved with transfusion).
• Direct bilirubin ≤2.5 mg/dL or 3x ULN (whichever is higher).
• 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.
• Respiratory rate:
• \<30 breaths per minute for patients aged \<18 years

You may not qualify if:

• 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 protocol treatment.
• For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to initiating protocol treatment.
• Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days prior to initiating protocol treatment.
• Exposure to chemotherapy or immunomodulatory medications within the last 2 weeks prior to initiating protocol 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: NA
• 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: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)