Know Cancer

forgot password

Phase II Trial Using Aldesleukin (IL-2) Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma

Phase 2
18 Years
Not Enrolling
Melanoma (Skin)

Thank you

Trial Information

Phase II Trial Using Aldesleukin (IL-2) Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma



- Determine tumor regression in patients with metastatic melanoma treated with
nonmyeloablative lymphodepleting chemotherapy comprising cyclophosphamide and
fludarabine followed by autologous CD25-positive-T-regulatory-cell-depleted lymphocyte
reinfusion and high-dose interleukin-2.


- Determine the rate of repopulation of CD25-positive T-regulatory cells in patients
treated with this regimen.

- Determine the toxicity of this regimen in these patients.


- Apheresis and CD25-positive T-regulatory cell depletion: Patients undergo 1-2 aphereses
to collect peripheral blood mononuclear cells (PBMC). CD25-positive T-regulatory cells
are depleted from the collected PBMC in vitro.

- Nonmyeloablative lymphodepleting chemotherapy: Patients receive cyclophosphamide IV
over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on days -6 to -2.

- Autologous CD25-positive-T-regulatory-cell-depleted lymphocyte reinfusion: Patients
receive autologous lymphocytes IV over 20-30 minutes on day 0.

- Filgrastim (G-CSF) and high-dose interleukin-2 (IL-2) therapy: Patients receive G-CSF
subcutaneously (SC) daily beginning on day 0 and continuing until blood counts recover.
Patients also receive high-dose IL-2 IV over 15 minutes 3 times daily on days 0-4 and
14-18. Patients are reevaluated 4-6 weeks after completion of high-dose IL-2 therapy.
Patients achieving stable disease or a partial response may receive additional
high-dose IL-2 as above for up to 2 retreatment courses in the absence of disease
progression or unacceptable toxicity. Retreatment begins at least 6 weeks after
autologous lymphocyte reinfusion.

After completion of study treatment, patients are followed at 4-6 weeks and then every 1-2
months thereafter.

PROJECTED ACCRUAL: A total of 16-29 patients will be accrued for this study within 1-1.5

Inclusion Criteria


- Diagnosis of melanoma

- Metastatic disease

- Measurable disease

- HLA-A2 negative disease

- Disease did not respond to OR recurred after completion of prior high-dose
interleukin-2 (IL-2)

- Eligible to receive high-dose IL-2

- No tumor reactive cells available for cell transfer therapy



- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- At least 3 months


- Absolute neutrophil count > 1,000/mm^3

- Platelet count > 100,000/mm^3

- Hemoglobin > 8.0 g/dL

- No coagulation disorders


- ALT and AST < 3 times upper limit of normal

- Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL if due to Gilbert's syndrome)

- Hepatitis B surface antigen negative

- Hepatitis C antigen negative


- Creatinine ≤ 2.0 mg/dL

- No renal failure requiring dialysis due to toxic effects of prior IL-2 administration


- No myocardial infarction

- No cardiac arrhythmias

- No other major cardiovascular illness as evidenced by a positive stress thallium or
comparable test

- Normal cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine
echocardiogram) AND LVEF ≥ 45% (for patients ≥ 50 years of age or who have a history
of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmias)


- No obstructive or restrictive pulmonary disease

- No other major respiratory illness

- FEV_1 ≥ 60% of predicted (for patients with a prolonged history of cigarette smoking
or symptoms of respiratory dysfunction)


- HIV negative

- Epstein-Barr virus positive

- No active systemic infection

- No autoimmune disease (e.g., autoimmune colitis or Crohn's disease)

- No immunodeficiency due to prior chemotherapy or radiotherapy

- Recovered immune competence after prior chemotherapy or radiotherapy as
evidenced by normal lymphocyte count and WBC and an absence of opportunistic

- No other major immune system disease


- Not pregnant or nursing

- Negative pregnancy test

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

- No other toxic effects during prior IL-2 administration that would preclude redosing
with IL-2, including the following:

- Mental status changes that would require intubation

- Bowel perforation


Biologic therapy

- See Disease Characteristics

- At least 4 weeks since prior systemic therapy


- At least 6 weeks since prior nitrosoureas

- At least 4 weeks since prior systemic therapy

Endocrine therapy

- No concurrent systemic steroid therapy


- Not specified


- Not specified

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor regression

Safety Issue:


Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Surgery Branch


United States: Food and Drug Administration

Study ID:




Start Date:

July 2005

Completion Date:

April 2007

Related Keywords:

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



Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182
NCI - Surgery Branch Bethesda, Maryland  20892-1201