Autologous Tumor Infiltrating Lymphocytes With Interleukin-2 for the Treatment of Locally Advanced, Recurrent or Metastatic Gastrointestinal Stromal Tumors

A Phase 2 Study to Evaluate the Efficacy and Safety of Adoptive Transfer of Autologous Tumor Infiltrating Lymphocytes in Patients With Unresectable, Recurrent, or Metastatic Gastrointestinal Stromal Tumors

This phase II trial tests the effect of autologous tumor infiltrating lymphocytes (TILs) in combination with interleukin-2 (aldesleukin) in treating patients with gastrointestinal stromal tumors (GIST) that has spread to nearby tissue or lymph nodes (locally advanced), that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Autologous TILs are made using the patient's own tumor cells collected from a previous surgery. Lymphocytes (a type of white blood cell) are a part of the immune system that helps the body fight infections. Lymphocytes are found in tumor tissue cells because they are working to attack the tumor. The cells from the tumor are grown in a lab to create more immune cells (lymphocytes). This may help the immune system find and destroy any remaining tumor cells. Aldesleukin is a form of interleukin-2, a cytokine made by leukocytes, that is made in the laboratory. Aldesleukin may help white blood cells and T cells regulate the immune response. Chemotherapy, such as cyclophosphamide and fludarabine, are given before receiving TIL to help kill tumor cells in the body and helps make room for the treatment. Colony-stimulating factors, such as filgrastim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving autologous TILs in combination with aldesleukin may be safe, tolerable, and/or effective in treating patients with locally advanced, recurrent or metastatic GIST.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Gastrointestinal Stromal Tumor; Locally Advanced Gastrointestinal Stromal Tumor; Unresectable Malignant Gastrointestinal Stromal Tumor; Recurrent Gastrointestinal Stromal Tumor; Refractory Malignant Gastrointestinal Stromal Tumor
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Filgrastim; Procedure: Positron Emission Tomography; Biological: Aldesleukin; Procedure: Multigated Acquisition Scan; Procedure: Chest Radiography; Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: Surgical Procedure; Biological: Tumor Infiltrating Lymphocyte Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with locally advanced, recurrent, or metastatic gastrointestinal stromal tumor (GIST) using the objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To further evaluate the efficacy of this therapy using complete response (CR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

II. To characterize the safety profile of this therapy in patients with locally advanced, recurrent, or metastatic gastrointestinal stromal tumors (GIST).

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -2 and TIL IV over 20-30 minutes on day 0 in the absence of disease progression or unacceptable toxicity. Starting within 24 hours of TIL infusion, patients receive aldesleukin IV over 15 minutes every 8 hours for up to 6 doses on days 0-3 in the absence of disease progression or unacceptable toxicity. Starting on day 1 or day 2, patients may receive filgrastim subcutaneously (SC) until neutrophil count > 1 x 10^9/L for 3 consecutive days or > 5 x 10^9/L. Patients with stable disease, partial response or recurrence may receive a second course of treatment. Patients also undergo chest x-ray at screening and urine and blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) throughout the study. Additionally, patients may also undergo echocardiography or multigated acquisition scan (MUGA) at screening and may also undergo a second surgery to collect cells on study.

After completion of study treatment, patients are followed up at 4-6 weeks, 12 weeks, every 3 months for 3 visits, then every 6 months up to month 24.

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: The Ohio State University Comprehensive Cancer Center; Phone Number: 1-800-293-5066; Email: OSUCCCClinicaltrials@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
      • Principal Investigator: Joal Beane, MD
      • Contact: Joal Beane, MD; Phone Number: 812-453-6178; Email: Joal.Beane@osumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Measurable locally advanced, recurrent, or metastatic GIST
• Patients with locally advanced disease should be unresectable by conventional surgical approaches
• Patients with distant metastatic spread must be refractory to approved standard systemic therapies (such as imatinib and sunitinib) if they are eligible to receive these treatments
• Patients must be co-enrolled on the companion protocol Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies (institutional review board [IRB] #2024C0043), and have available TIL cultures for therapy
• Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible
• Greater than or equal to 18 years of age and less than or equal to age 75
• Able to understand and sign the informed consent document
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Life expectancy of greater than three months
• Patients of both genders who are of child-bearing potential must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the treatment

• Serology:

  • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcriptase-polymerase chain reaction (RT-PCR) and be HCV ribonucleic acid (RNA) negative
• Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus
• Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim
• White blood cells (WBC) ≥ 3000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin > 8.0 g/dl
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ to 3.5 times the upper limit of normal
• Serum creatinine ≤ to 1.6 mg/dl and calculated creatinine clearance (Crockcroft-Gault or 24-hour urine creatinine) ≥ 30 mL/min
• Total bilirubin ≤ to 2.0 mg/dl, except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl

• More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo)

  • Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less

Exclusion Criteria:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant
• Any form of primary immunodeficiency (such as severe combined immunodeficiency disease)
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
• Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses
• History of major organ autoimmune disease
• Concurrent systemic steroid therapy including physiologic replacement dosing of systemic steroids (i.e. prednisone ≤ 10 mg/day or equivalent) as well as topical or inhaled corticosteroids are not allowed
• History of severe immediate hypersensitivity reaction to any of the agents used in this study
• History of active coronary or ischemic symptoms

• Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%

  • Note: testing is required in patients with:

    • Age ≥ 65 years old

    • Clinically significant atrial and or ventricular arrhythmias including but not limited to:

      • Atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain

• Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60% predicted tested in patients with:

  • A prolonged history of cigarette smoking (20 pack [pk]/year of smoking within the past 2 years)
  • Symptoms of respiratory dysfunction
• Patients who are receiving any other investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (TIL, aldesleukin); Patients receive cyclophosphamide IV over 2 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -2 and TIL IV over 20-30 minutes on day 0 in the absence of disease progression or unacceptable toxicity. Starting within 24 hours of TIL infusion, patients receive aldesleukin IV over 15 minutes every 8 hours for up to 6 doses on days 0-3 in the absence of disease progression or unacceptable toxicity. Starting on day 1 or day 2, patients may receive filgrastim SC until neutrophil count > 1 x 10^9/L for 3 consecutive days or > 5 x 10^9/L. Patients with stable disease, partial response or recurrence may receive a second course of treatment. Patients also undergo chest x-ray at screening and urine and blood sample collection, CT, MRI or PET throughout the study. Additionally, patients may also undergo echocardiography or MUGA at screening and may also undergo a second surgery to collect cells on study.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Asta B 518; B-518; WR-138719; B 518; B518; WR 138719; WR138719; Drug: Fludarabine; Given IV; Other Names: Fluradosa; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Filgrastim-aafi; Nivestym; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Filgrastim Biosimilar Filgrastim-sndz; Zarxio; Filgrastim XM02; Tbo-filgrastim; Granix; Nivestim; XM02; Filgrastim-sndz; Filgrastim Biosimilar Tbo-filgrastim; Filgrastim-ayow; Releuko; Neutroval; Procedure: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Biological: Aldesleukin; Given IV; Other Names: Proleukin; 125-L-Serine-2-133-interleukin 2; r-serHuIL-2; Recombinant Human IL-2; Recombinant Human Interleukin-2; Procedure: Multigated Acquisition Scan; Undergo MUGA; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan; RNV Scan; Procedure: Chest Radiography; Undergo chest x-ray; Other Names: Chest X-ray; Procedure: Biospecimen Collection; Undergo urine and blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Echocardiography Test; Undergo echocardiography; Other Names: Echocardiography; EC; Procedure: Surgical Procedure; Undergo a second surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS; Biological: Tumor Infiltrating Lymphocyte Therapy; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Will be estimated by the proportion of patients with a best response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors criteria, with corresponding exact 95% confidence limit being reported.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate	Will be estimated by the proportion of patients with a best response of complete response (CR) by Response Evaluation Criteria in Solid Tumors criteria	Up to 24 months
Duration of response	The distribution among patients achieving CR or PR will be characterized by median and quartiles.	Up to 24 months
Disease control rate		Up to 24 months
Progression-free survival	Will be estimated by the Kaplan-Meier method. The corresponding median survival times (with 95% confidence limits) will be determined, as will the cumulative percentage of patients remaining progression-free (and the cumulative percentage-alive) at selected time points after initial treatment (e.g., 3, 6,12, 18 months).	From the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression), assessed up to 24 months
Overall survival	Will be estimated by the Kaplan-Meier method. The corresponding median survival times (with 95% confidence limits) will be determined, as will the cumulative percentage of patients remaining progression-free (and the cumulative percentage-alive) at selected time points after initial treatment (e.g., 3, 6,12, 18 months).	From the initial date of treatment to the recorded date of death, assessed up to 24 months
Incidence of adverse events	Will be described and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade.	Up to 30 days after treatment

Collaborators and Investigators

• Sponsor: Joal Beane
• Investigators: Principal Investigator: Joal Beane, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hydrocarbons; Biological Factors; Carbohydrates; Physical Phenomena; Chemistry Techniques, Analytical; Spectrum Analysis; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Cyclophosphamide; Specimen Handling; Magnetic Resonance Spectroscopy; fludarabine; aldesleukin; Surgical Procedures, Operative; X-Rays; Granulocyte Colony-Stimulating Factor; Filgrastim
• Other Study ID Numbers: OSU-22356 (Other Identifier: Ohio State University Comprehensive Cancer Center); NCI-2026-03863 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No