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A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma

Phase 2
18 Years
Open (Enrolling)
Melanoma (Skin)

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Trial Information

A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma



- Determine the ability of treatment with short-term cultured autologous
tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a
nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide
and fludarabine phosphate to mediate tumor regression in patients with metastatic

- Determine the toxicity of this treatment regimen.


- Determine the rate of repopulation of the young TIL cells.

- Establish in vitro immunological correlates that predict in vivo persistence and
clinical response.


- Conditioning regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and
-6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.

- Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients
receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. Patients
also receive high-dose aldesleukin IV over 15 minutes every 8 hours on days 0-4.

Patients with stable disease, partial response, or recurrent disease after initial response
may receive 1 additional course of treatment (as above) beginning 8 weeks after completion
of aldesleukin.

Blood samples are collected at baseline, at 1 week and 1 month after TIL infusion, and then
periodically thereafter for research studies. Samples are analyzed for differences in
function and phenotype prior to and after TIL infusion. The immunological correlates of
treatment are also evaluated using FACS, cytokine release assays, ELISPOT assays, flow
cytometry, and PCR. TIL that are cryopreserved at the time of infusion are analyzed to
determine cell phenotype and function; correlation of in vitro characteristics of the
infused cells with in vivo antitumor activity; and the activity, specificity, and telomere
length using flow FISH.

After completion of study treatment, patients are followed at 4-6 weeks, every 3 months for
1 year, every 6 months for 2 years, and then annually for 2 years.

Inclusion Criteria


- Diagnosis of metastatic melanoma

- Refractory to standard treatment including high-dose aldesleukin (IL-2), unless
previously ineligible for or refused IL-2

- Measurable disease with ≥ 1 lesion that is resectable for tumor-infiltrating
lymphocyte generation

- Patients with ≥ 1 brain metastases < 1 cm each, or 1-2 brain metastases > 1 cm are
eligible provided they have been treated and stable for ≥ 3 months


- ECOG performance status 0-1

- Life expectancy > 3 months

- ANC > 1,000/mm^3 (without filgrastim support)

- WBC > 3,000/mm^3

- Hemoglobin > 8.0 g/dL

- Platelet count > 100,000/mm^3

- Serum ALT/AST < 3 times upper limit of normal

- Total bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)

- Serum creatinine ≤ 1.6 mg/dL

- LVEF > 45% in patients meeting the following criteria:

- Clinically significant atrial and/or ventricular arrhythmias, including, but not
limited to, atrial fibrillation, ventricular tachycardia, or second- or
third-degree heart block

- At least 60 years of age

- FEV_1 > 60% in patients meeting the following criteria:

- Prolonged history of cigarette smoking

- Symptoms of respiratory dysfunction

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 months after
completion of study treatment

- No HIV or hepatitis B or C positivity

- No form of primary immunodeficiency (e.g., severe combined immunodeficiency disease
or AIDS)

- No opportunistic infections

- No active systemic infections

- No history of severe immediate hypersensitivity reaction to any of the agents used in
this study

- No coagulation disorders

- No myocardial infarction, cardiac arrhythmias, or positive stress thallium or
comparable test

- No history of coronary revascularization or ischemic symptoms

- No obstructive or restrictive pulmonary disease

- No other active major medical illness of the cardiovascular, respiratory, or immune


- See Disease Characteristics

- Recovered from prior therapy (alopecia or vitiligo allowed)

- At least 6 weeks since prior ipilimumab

- Must have normal colonoscopy with normal colonic biopsies

- At least 4 weeks since prior systemic therapy

- Minor surgical procedures within the past 3 weeks allowed provided all toxicities
have recovered to ≤ grade 1

- No concurrent systemic steroids

- No other concurrent experimental agents

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Primary Objective

Outcome Description:

Determine the ability of autologous cells infused with minimal in vitro culture in conjunction with high dose interleukin -2 (IL-2) following non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.

Outcome Time Frame:

4-6 weeks after completion of TIL

Safety Issue:


Principal Investigator

John P. Hanson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Luke's Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

February 2009

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma



Aurora St. Luke's Medical Center Milwaukee, Wisconsin  53215