Treatment of Metastatic Melanoma With Tumor Infiltrating Lymphocytes and IL-2 Following Lympho-depleting Chemotherapy

NCT00604136 | Unknown Phase 2 DMC

• 1 other identifier: MS269- HMO-CTIL
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Prior preclinical and clinical studies have shown that tumors from patients with advanced melanoma contain tumor-infiltrating lymphocytes (TIL) with anti-tumor reactivity. These TIL can be expanded in the laboratory to large numbers, and reinfused to the patient. Using a chemotherapy regimen that selectively kills lymphocytes, a single institution Phase II study of 35 patients showed a 51% objective response rate to TIL and interleukin-2 injection. In the present trial we would like to investigate whether we can achieve similar results in a Hadassah Phase II study, and to determine the feasibility of applying this approach to patients with advanced melanoma who currently have few treatment options.

Conditions

Metastatic Melanoma

Keywords

melanoma; tumor infiltrating lymphocytes; interleukin-2

Outcome Measures

Primary Outcomes (1)

• To determine the response rate of this approach when administered in our hospital

  Two years

Interventions

tumor infiltrating lymphocytes BIOLOGICAL

Patients will have a melanoma metastasis resected and cultured in IL-2 in vitro. Tumor infiltrating lymphocytes from these cultures will be assessed for tumor reactivity and those with such activity will be further expanded and adoptively transferred. Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 mg/kg/day x2 days IV)and fludarabine (25 mg/mE2/day IV x5days). Following this regimen, patients will receive an intravenous adoptive transfer of at least 10E9 tumor-reactive lymphocytes followed by high dose IL-2 (720,000 IU/kg/dose IV every 8 hours for up to 15 doses).

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 metastatic melanoma with a resectable metastatic lesion of sufficient size and be willing to undergo such a resection for experimental purposes. For HLA-A0201+ patients, lesions must be \> 1.5 cm in diameter and for HLA-A0201- patients, lesions must be \> 3 cm in diameter.
• Patients must be \> 18 years of age and must have measurable metastatic melanoma (in addition to the resected lesion).
• Patients of both genders must be willing to practice birth control during treatment and for four months after receiving the preparative regimen.
• Clinical performance status of ECOG 0, 1.
• Absolute neutrophil count greater than 1000/mm3 without support of filgrastim.
• Platelet count greater than 100,000/mm3.
• Serum ALT/AST less than three times the upper limit of normal.
• Serum creatinine less than or equal to 1.6 mg/dl.
• Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.
• Patients must be able to understand and sign the Informed Consent document

You may not qualify if:

• Less than 4 weeks has elapsed since any prior systemic therapy or less than six weeks since prior nitrosourea therapy
• Women who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Life expectancy of less than three months.
• Patients who have received prior treatment with anti-CTLA-4 antibody will be excluded unless a post anti-CTLA-4 antibody treatment colonoscopy was normal with normal colonic biopsies.
• Patients who require immediate active treatment for symptomatic CNS lesions will not be eligible until after treatment of their symptomatic lesions.
• Less than 4 weeks has elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, or less than six weeks since prior nitrosourea therapy. All patients' toxicities must have recovered to a grade 1 or less or as specified in the eligibility criteria. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria.
• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Life expectancy of less than three months.
• Requirement for systemic steroid therapy.
• Hemoglobin less than 8g/dl unable to be corrected with transfusion.
• Any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by normal ANC \> 1000/mm3 and absence of 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.)
• Seropositive 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 are less responsive to the experimental treatment and more susceptible to its toxicities.)
• Patients with hepatitis B or hepatitis C will be excluded.
• The following patients will be excluded because of inability to receive high dose interleukin-2:

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Organization, Jerusalem, Israel

Jerusalem, 91120, Israel

RECRUITING

MeSH Terms

Conditions

Melanoma

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

Central Study Contacts

Michal Lotem, MD

CONTACT

972508573528; mlotem@hadassah.org.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 30, 2008
• Study Start: July 1, 2008
• Primary Completion: December 1, 2019
• Study Completion: July 1, 2020
• Last Updated: September 18, 2018

Record last verified: 2018-09

Locations

IL (1)