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

• Status: Recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Iovance Biotherapeutics, Inc.; National Cancer Institute (NCI); The V Foundation for Cancer Research
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2

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 (PCR).

• 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 excluded

• 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