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


N/A
18 Years
N/A
Open (Enrolling)
Both
Metastatic Melanoma

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Trial Information

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


Patients are being offered admission to this study to test the side effects of an
investigational treatment prepared from special immune cells (T cells) specific for
melanoma. A T-cell is a type of lymphocyte. Lymphocytes are a type of white blood cell that
protect people from viral infections; help other cells fight bacterial and fungal
infections; produce antibodies; fight cancers; and coordinate the activities of other cells
in the immune system. These special immune cells will be taken from a sample of the
patient's tumor tissue that will be surgically removed from their body and grown in the
laboratory. They will then given back to the patient in their veins. These cells are called
tumor infiltrating lymphocytes (TIL). We wish to study the side effects of TIL when they are
given with two chemotherapy drugs to temporarily decrease the patient's own immune cells and
a drug called Interleukin-2 (IL-2). The two chemotherapy drugs called fludarabine and
cytoxan are used to greatly reduce the number of normal lymphocytes circulating in the
patient's body, called lymphodepletion, so that there will be more "space" for the cancer
fighting lymphocytes (T-cells) that will be infused in their veins. We wish to find out how
often these cells can shrink or slow the growth of the patient's melanoma. We also wish to
find out the effects of lymphodepletion followed by TIL and high dose IL-2 on the patient's
immune system. The lymphodepletion followed by TIL and high dose IL-2 is experimental, and
has not been proven to help treat melanoma.

The IL-2 has been approved by the Food and Drug Administration (FDA) for the treatment of
metastatic melanoma that cannot be surgically removed. The chemotherapy drugs cytoxan and
fludarabine used for lymphodepletion have been approved by the FDA, but not for the
treatment of metastatic melanoma.

The combination of lymphodepletion followed by TIL and high dose IL-2 is not FDA approved
but the FDA is permitting its use in this study.


Inclusion Criteria:



- 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.

Exclusion Criteria:

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants Who Can Grow and Expand T-Cells

Outcome Description:

Feasibility is the primary endpoint of this trial, which is defined as a patient who can grow and expand T-cells. We anticipate that this is feasible for at least 50% of the eligible patients. If it is feasible for seven/six or more patients out of 16 eligible patients, then we will consider to reject a feasibility rate of no more than 25%/20% in favor of at least 50% for a one-sided type I error of 0.08/0.082 and type II error of 0.227/0.105.

Outcome Time Frame:

Average of 10 Months

Safety Issue:

No

Principal Investigator

Amod Sarnaik, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

MCC-15781

NCT ID:

NCT01005745

Start Date:

October 2009

Completion Date:

December 2013

Related Keywords:

  • Metastatic Melanoma
  • skin
  • Melanoma

Name

Location

H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612