Clinical trial NCT00303836: Vaccine Therapy With or Without Interleukin-2 After Chemotherapy and an Autologous White Blood Cell Infusion in Treating Patients With Metastatic Melanoma
Official title: A Phase II Study Using a Peptide Vaccine With or Without Aldesleukin Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Melanoma
Stage IV Melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-03-17
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II trial is studying how well giving vaccine therapy with or without interleukin-2 after chemotherapy and an autologous white blood cell infusion works in treating patients with metastatic melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy with interleukin-2, chemotherapy, and an autologous white blood cell infusion may be a more effective treatment for metastatic melanoma.

Detailed description: PRIMARY OBJECTIVES:

I. Determine the ability of gp100 and MART-1 peptide vaccines with or without a high-dose interleukin-2 (IL-2), when administered after a nonmyeloablative, lymphodepleting preparative regimen and reinfusion of autologous CD25+ T-regulatory-depleted lymphocytes, to mediate tumor regression in patients with metastatic melanoma.

SECONDARY OBJECTIVES:

I. Determine the generation of antitumor lymphocytes and the rate of repopulation of CD25+ T-regulatory cells in patients treated with this regimen.

II. Determine the toxicity of this treatment regimen.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo apheresis and in-vitro depletion of T-regulatory cells. Patients then receive a nonmyeloablative, lymphocyte-depleting preparative regimen comprising cyclophosphamide IV over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on days -6 to -2 followed by autologous T-regulatory-depleted lymphocytes IV over 20-30 minutes on day 0. Patients receive vaccination with gp100:209-217 (210M) and MART-1:27-35 peptides emulsified in Montanide ISA-51 subcutaneously (SC) on days 0-3, 20-23, 41-44, and 62-65. Patients also receive filgrastim (G-CSF) SC beginning on day 1 and continuing until blood counts recover.

ARM II: Patients receive treatment as in arm I. Patients also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0-4, beginning after the lymphocyte infusion. IL-2 treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 1-3 months.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of metastatic melanoma

  * No tumor reactive cells available for cell transfer therapy
* Measurable disease
* Previously treated with interleukin-2 (IL-2) and meets 1 of the following criteria:

  * No response (progressive disease)
  * Recurrent disease
* HLA\*0201 positive
* ECOG performance status 0 or 1
* Absolute neutrophil count \> 1,000/mm\^3
* Platelet count \> 100,000/mm\^3
* Hemoglobin \> 8.0 g/dL
* ALT and AST \< 3 times upper limit of normal
* Bilirubin ≤ 2.0 mg/dL (\< 3.0 mg/dL if Gilbert's disease is present)
* Creatinine ≤ 2.0 mg/dL
* Life expectancy ≥ 3 months
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for up to 4 months after receiving the preparative regimen
* No active systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular, respiratory, or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, or obstructive or restrictive pulmonary disease
* No autoimmune disease (e.g., autoimmune colitis or Crohn's disease) or primary immunodeficiency disease
* No HIV positivity
* No hepatitis B or C virus positivity
* No Epstein-Barr virus negativity
* Eligible to receive high-dose IL-2, as evidenced by the following:

  * Patients ≥ 50 years of age must have a normal cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) AND LVEF ≥ 45%
  * Patients with a history of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmias must have a normal cardiac stress test AND LVEF ≥ 45%
  * Patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test, as evidenced by FEV 1 ≥ 60% of predicted
* At least 4 weeks since prior systemic therapy
* At least 6 weeks since prior nitrosourea therapy
* No concurrent systemic steroid therapy
* Recovered immune competence after prior chemotherapy or radiotherapy
* No prior gp100:209-217 or MART-1:27-35 peptide vaccine

Primary outcomes:
measure: Objective clinical response (CR or PR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Presence of anti-tumor T cells
timeFrame: Up to 2 years
measure: Recovery of regulatory T cells
timeFrame: Up to 2 years
measure: Incidence of DLTs and SAEs graded according to CTCAE version 3.0
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Cancer Institute Surgery Branch
state: Maryland
Study officials:
affiliation: National Cancer Institute Surgery Branch
name: Steven Rosenberg
role: PRINCIPAL_INVESTIGATOR
References: