Clinical Trials /

Lymphodepletion Plus Adoptive Cell Therapy With High Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma



This is a single-arm trial that will evaluate the safety and feasibility of the Tumor-infiltrating lymphocyte (TIL) treatment and the persistence of TIL survival in vivo following treatment

Related Conditions:
  • Soft Tissue Sarcoma
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: Lymphodepletion Plus Adoptive Cell Therapy With High Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma
  • Official Title: A Phase I Trial of Lymphodepletion Plus Adoptive Cell Therapy With High-Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: MCC-19837
  • SECONDARY ID: 1K08CA252642-01
  • NCT ID: NCT04052334


  • Sarcoma


TILTumor-infiltrating lymphocytesInfusion of Tumor-infiltrating lymphocyte
Interleukin-2IL-2Infusion of Tumor-infiltrating lymphocyte
FludarabineFludaraInfusion of Tumor-infiltrating lymphocyte
CyclophosphamideCytoxan, NeosarInfusion of Tumor-infiltrating lymphocyte


This is a single-arm trial that will evaluate the safety and feasibility of the Tumor-infiltrating lymphocyte (TIL) treatment and the persistence of TIL survival in vivo following treatment

Trial Arms

Infusion of Tumor-infiltrating lymphocyteExperimentalParticipants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m^2 intravenous piggyback (IVPB). All participants will receive not less than 10^9, and up to 1x10^12 T cells in ≥250 mL NS as an inpatient by intravenously (IV). Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an intravenous bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
  • TIL
  • Interleukin-2
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must fulfill all of the following criteria to be eligible for the study
             at the time of tumor resection and initiation of TIL expansion.

          -  Stated willingness to comply with all study procedures and availability for the
             duration of the study

          -  Participants must have metastatic, high-grade soft tissue sarcoma, all subtypes will
             be eligible

          -  Residual measurable disease after resection of target lesion(s) for TIL growth

          -  Eastern Cooperative Oncology Group (ECOG) 0 to 1. ECOG performance status of 0 to 1
             will be inferred if the patient's level of energy is ≥ 50% of baseline.

          -  Participants must have progressed on at least one prior standard of care treatment
             regimen for metastatic disease.

          -  A negative pregnancy test (urine or serum) must be documented at screening for women
             of childbearing potential.

          -  A MUGA scan (ejection fraction > 50% is required) ≤ 6 months prior to lymphodepletion.

          -  Pulmonary function tests should be completed ≤ 6 months prior to lymphodepletion and
             forced expiratory volume (FEV1) > 65% or FVC > 65% of predicted are required

          -  Adequate renal, hepatic, and hematologic function, including creatinine of ≤ 1.7
             gm/dL, total bilirubin ≤ 2.0 mg/dL, except in patients with Gilbert's Syndrome who
             must have a total bilirubin less than 3.0 mg/dL, AST and ALT of less than 3 X
             institutional upper limit of normal, hemoglobin of 8 gm/dL or more, white blood cells
             of 3000 per mm^3 and total granulocytes of 1000 per mm^3 or more, and platelets of 100
             000 per mm^3 or more.

          -  Participants must have a positive screening EBV antibody titre on screening test.

          -  Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the
             participant agrees to continue to use a method of contraception throughout the study
             such as: barrier (i.e. condom, diaphragm), hormonal, IUD, or sponge plus spermicide.

          -  Prothrombin time (PT) and partial thromboplastin time (PTT) within 1.5 times the
             institutional upper limit of normal

          -  Participants with echocardiogram (EKG) within 14 days of initiation of chemotherapy
             demonstrating no new rhythm, axis, or ST segment

          -  Urinalysis within 14 days demonstrating no evidence of a urinary tract infection.

        Exclusion Criteria:

          -  Participants with active systemic infections requiring intravenous antibiotics,
             coagulation disorders, or other major medical illnesses of the cardiovascular,
             respiratory, or immune system are excluded.

          -  Participants testing positive for HIV titer, hepatitis B surface antigen, human T-cell
             leukemia-lymphoma virus (HTLV) I or II antibody, or both rapid plasma regain (RPR) and
             fluorescent treponemal antibody (FTA) are excluded. Participants with hepatitis C
             antibody must have a negative (undetectable) viral load by polymerase chain reaction

          -  Participants who are pregnant or nursing are excluded.

          -  Participants needing chronic immunosuppressive systemic steroids are excluded

          -  Participants with autoimmune diseases that require immunosuppressive medications are

          -  Presence of a significant psychiatric disease, which in the opinion of the principal
             investigator or his designee, would prevent adequate informed consent or render
             immunotherapy unsafe or contraindicated

          -  Participants with central nervous system metastases will be excluded.

          -  Inability to comprehend and give informed consent
Maximum Eligible Age:39 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants who experienced Serious Adverse Events and Adverse Events
Time Frame:Baseline to 12 months
Safety Issue:
Description:Participants able to safely tolerate preparatory lymphodepletion, infusion of tumor-infiltrating lymphocytes (TIL) and subsequent IL-2, as measured by adverse events and serious adverse events.

Secondary Outcome Measures

Measure:Number of participants with objective antitumor response
Time Frame:At 12 weeks
Safety Issue:
Description:Number of participants with objective response (Complete Response (CR) + Progressive Response (PR)) rate at 12 weeks following TIL infusion, as measured by RECIST v1.1
Measure:Number of participants with circulating tumor-infiltrating lymphocytes (TIL) product at 6 weeks
Time Frame:At 6 weeks
Safety Issue:
Description:Number of participants with persistence of TIL infusion product at 6 weeks following treatment, as measured by T-cell receptor repertoire comparison between the infusion product and circulating Peripheral blood mononuclear cell (PBMC).


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Soft Tissue Sarcoma
  • Adoptive Cell Therapy

Last Updated

July 13, 2021