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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04052334
Recruitment Status : Active, not recruiting
First Posted : August 9, 2019
Last Update Posted : June 5, 2023
Iovance Biotherapeutics, Inc.
The V Foundation for Cancer Research
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief 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

Condition or disease Intervention/treatment Phase
Sarcoma Drug: TIL Drug: Interleukin-2 Drug: Fludarabine Drug: Cyclophosphamide Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 27, 2019
Actual Primary Completion Date : May 16, 2023
Estimated Study Completion Date : May 16, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Fludarabine

Arm Intervention/treatment
Experimental: Infusion of Tumor-infiltrating lymphocyte

Participants 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.

Drug: TIL
Participants will receive an infusion of Tumor-infiltrating lymphocytes (TIL) after tumor resection and TIL product is generated.
Other Name: Tumor-infiltrating lymphocytes

Drug: Interleukin-2
Participants will receive Interleukin-2 (IL-2) 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Other Name: IL-2

Drug: Fludarabine
Participants will receive an intravenously (IV) infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Other Name: Fludara

Drug: Cyclophosphamide
Participants will receive Cyclophosphamide 60 mg/kg/day intravenously (IV) in 250 mL normal saline (NS) over approximately 2 hours, 7 days prior to T-Cell infusion
Other Names:
  • Cytoxan
  • Neosar

Primary Outcome Measures :
  1. Number of participants who experienced Serious Adverse Events and Adverse Events [ Time Frame: Baseline to 12 months ]
    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 :
  1. Number of participants with objective antitumor response [ Time Frame: At 12 weeks ]
    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

  2. Number of participants with circulating tumor-infiltrating lymphocytes (TIL) product at 6 weeks [ Time Frame: At 6 weeks ]
    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).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  • Participants that have had previously grown sterile, validated TILs under good manufacturing practice conditions meeting the above criteria are eligible using the previously established TIL product stored in the Cell Therapies Core facility for up to 2 years after harvesting.
  • 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 If new ST changes are present, patients may be included if cardiac stress test indicates no evidence of inducible cardiac ischemia.
  • Urinalysis within 14 days demonstrating no evidence of a urinary tract infection.
  • Participants with evidence of ongoing disease regression that is attributed to a therapy that is not part of the trial and that was administered after TIL harvest and expansion but prior to adoptive transfer of TILs should continue on prior therapy and may be treated with TIL only if their disease is stable or there is evidence of progressive disease. In this event as described above, the TIL will be frozen and stored for future use, in the event of progression, prior to the rapid expansion step.

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 that have completed a chemotherapy regimen given with the intent of lymphodepletion or cellular immunotherapy which included non-myeloablative lymphodepletion strategy.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04052334

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United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Iovance Biotherapeutics, Inc.
The V Foundation for Cancer Research
National Cancer Institute (NCI)
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Principal Investigator: John Mullinax, MD Moffitt Cancer Center
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT04052334    
Other Study ID Numbers: MCC-19837
1K08CA252642-01 ( U.S. NIH Grant/Contract )
First Posted: August 9, 2019    Key Record Dates
Last Update Posted: June 5, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Soft Tissue Sarcoma
Adoptive Cell Therapy
Additional relevant MeSH terms:
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Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents