Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma

NCT01005745 | Completed Results DMC

• 1 other identifier: MCC-15781
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The overall purpose of this research study is to find a better way to treat melanoma. This will be a single arm exploratory trial to evaluate prospectively the feasibility of, the toxicities of, and the persistence of TIL which can survive in vivo.

Conditions

Metastatic Melanoma

Keywords

skin; adoptive cell therapy; tumor-infiltrating lymphocytes (TIL); lymphodepletion

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Tumor Infiltrating Lymphocytes (TIL) Growth

  Feasibility was the primary endpoint of this trial, defined as a patient who can grow and expand T-cells: Number of participants with fragments cultured; Number of participants with fragments that reached a final count of 20e6 cells within 5 weeks of culture; Number of participants with fragments that reached a final count of 20e6 cells within 5 weeks of culture and were cocultured with autologous or human leukocyte antigen (HLA)-matched tumor cells for interferon(IFN)-γ production; Number of participants with fragments that produced IFN-γ in response to autologous or HLA-matched tumor cells.

  192 Days Post Surgical Resection

Secondary Outcomes (1)

• Number of Participants With Objective Response (OR)

  Average of 10 Months Follow-up

Study Arms (1)

TIL With High Dose IL-2

EXPERIMENTAL

Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hour infused intravenously over 24 hours. Day -5 to Day -1: Fludarabine 25 mg/m\^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days. Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused. Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.

Procedure: Surgery; Drug: Administration of Lymphodepletion; Other: Adoptive Cell Transfer; Drug: High Dose IL-2

Interventions

Adoptive Cell Transfer OTHER

T-cell infusion

TIL With High Dose IL-2

High Dose IL-2 DRUG

Beginning approximately 12 - 16 hours after cell infusion.

Also known as: Interleukin-2, Aldesleukin, Proleukin

TIL With High Dose IL-2

Surgery PROCEDURE

Surgery to remove a tumor for growth of TIL

Also known as: Tumor Infiltrating Lymphocytes (TIL), T-cell, lymphocyte

TIL With High Dose IL-2

Administration of Lymphodepletion DRUG

Lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T cell persistence and effectiveness in vivo

Also known as: Cytoxan

TIL With High Dose IL-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have unresectable metastatic stage IV melanoma or stage III in-transit or regional nodal disease.
• Residual measurable disease after resection of target lesion(s) for TIL growth
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 -1. ECOG performance status of 0-1 will be inferred if the patient's level of energy is ≥ 50% of baseline.
• Patients may be treatment-naïve or may have been previously treated for metastatic disease.
• Patients with a negative pregnancy test (urine or serum) must be documented at screening for women of childbearing potential (WOCBP).
• Adequate renal, hepatic and hematologic function, including creatinine of less than or equal to 1.7 gm/dL, total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL, aspartic transaminase (AST) and alanine transaminase (ALT) of less than 3X institutional upper limit of normal (ULN), hemoglobin of 8 gm/dL or more, white blood count (WBC) of 3000 per mm³ and total granulocytes of 1000 per mm³ or more, and platelets of 100,000 per mm³ or more.
• Patients must have a positive screening Epstein-Barr virus (EBV) antibody titre on screening test.
• Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics.
• Patients that had previously grown sterile, validated TIL under Good Manufacturing Practices (GMP) conditions on Moffitt Clinical trial protocol 15375 (Use of Excess Melanoma Tumor Specimens Not Required for Diagnostic Purposes for Validation of Tumor Infiltrating Lymphocyte \[TIL\] Growth Procedures) meeting the above criteria may be consented and enrolled in the current trial using the previously established TIL stored in the Cell therapies Core facility for up to 2 years.
• At screening, patients with ≤ 3 untreated central nervous system (CNS) metastases may be included provided none of the untreated lesions are \> 1 cm in greatest dimension, and there is no peri-tumoral edema present on brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\] if MRI is contraindicated).
• At screening, patients with CNS metastases treated with either surgical resection and/or radiation therapy may be included. Patients may be included if the largest lesion is ≤ 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment.
• At screening, patients may be included if the largest lesion is \> 1 cm or \> 3 in number, and there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy.
• All laboratory and imaging studies must be completed and satisfactory within 30 days of signing the consent document.

You may not qualify if:

• Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system are excluded.
• Patients testing positive for human immunodeficiency virus (HIV) titre, Hepatitis B surface antigen, Hepatitis C antibody, Human T-lymphotropic virus (HTLV) I or II antibody, or both rapid plasma reagent (RPR) and fluorescein treponemal antibodies (FTA) positive are excluded.
• Patients who are pregnant or nursing
• Patients needing chronic, immunosuppressive systemic steroids
• Patients with autoimmune diseases that require immunosuppressive medications
• 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
• Patients with \> 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded.
• Patients with ≤ 3 untreated CNS metastases but with at least one lesion \>1 cm or peri-tumoral edema will be excluded.
• Patients with treated CNS metastases \> 1 cm or \> 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy.
• Inability to comprehend and give informed consent

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Melanoma

Interventions

Surgical Procedures, Operative; Lymphocyte Count; Cyclophosphamide; Adoptive Transfer; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Leukocyte Count; Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Amod Sarnaik, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

amod.sarnaik@moffitt.org

813-745-8581

Study Officials

• Amod Sarnaik, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2009
• First Posted: November 2, 2009
• Study Start: October 20, 2009
• Primary Completion: January 31, 2014
• Study Completion: August 18, 2025
• Last Updated: December 19, 2025
• Results First Posted: June 2, 2014

Record last verified: 2025-12

Locations

US (1)