Vaccine Therapy Following Therapeutic Autologous Lymphocytes and Cyclophosphamide in Treating Patients With Metastatic Melanoma

Conditions:Skin Cancer
Therapuetic Areas:Oncology
Age Range:Any
Start Date:March 2012

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Phase I Study To Evaluate The Use Of Autologous T- Antigen-Presenting Cells (T-APC) To Enhance The Persistence Of Adoptively Transferred CD8+ Antigen-Specific T Cells (CTL) Following Cyclophosphamide Conditioning For Patients With Metastatic Melanoma

This phase I trial studies the side effects and best dose of autologous T-antigen-presenting
cells (T-APC) vaccine following therapeutic autologous lymphocytes (CTL) and
cyclophosphamide in treating patients with metastatic melanoma. Aldesleukin may stimulate
lymphocytes, such as CTL, to kill melanoma cells. Treating lymphocytes with aldesleukin in
the laboratory may help the lymphocytes kill more tumor cells when they are put back in the
body. Vaccines made from melanoma antigen may help the body build an effective immune
response to kill tumor cells and may boost the effect of the CTL. Drugs used in
chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor
cells, either by killing the cells or by stopping them from dividing. Giving T-APC vaccine
after CTL and cyclophosphamide may be an effective treatment for melanoma


I. Assess the safety and toxicity of T-APC vaccination following adoptive T cell therapy.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred
cytotoxic t lymphocytes (CTL) followed by T-APC vaccination.


I. Evaluate the antitumor effect of adoptive T cell therapy followed by T-APC vaccination.

OUTLINE : This is a dose-escalation study of T-APC vaccine.

INFUSION I: Patients receive high-dose cyclophosphamide intravenously (IV) on days -3 and -2
and low-dose aldesleukin (IL-2) subcutaneously (SC) twice daily (BID) on days 0-14. Patients
also receive CTL IV on day 0.

INFUSION II: Beginning 6-48 hours later, patients receive high-dose cyclophosphamide,
low-dose IL-2, and CTL as in Infusion I. Patients also receive T-APC vaccine IV within 18-36
hours following CTL infusion and in week 4, and IL-2 SC BID on days 0-14 following second
T-APC vaccination.

After completion of study treatment, patients are followed up for 8 weeks.

Inclusion Criteria:

- Histopathological documentation of melanoma concurrent with the diagnosis of
metastatic disease

- Tumor expression of melanocyte differentiation antigen (MDA: MART-1 = 2+ staining or
> 25%) by immunohistochemistry (IHC)

- Expression of human leukocyte antigen (HLA)-A201

- Zubrod performance status of '0-1' at the time of treatment

- Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic
imaging (X-ray, computed tomography [CT] scan)

- Normal cardiac stress test will be required for all patients with any history of
cardiac disease

Exclusion Criteria:

- Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception or abstinence; women of childbearing
potential must have a negative pregnancy test within two weeks prior to entry

- Serum creatinine > 1.6 mg/dL or Creatinine clearance < 75 ml/min

- Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3x upper limit of normal

- Bilirubin > 1.6 mg/dL

- Prothrombin time > 1.5 x control

- Clinically significant pulmonary dysfunction, as determined by medical history and
physical exam; patients so identified will undergo pulmonary functions testing and
those with forced expiratory volume in one second (FEV1) < 2.0 L or carbon monoxide
diffusing capacity (DLco) (corr for hemoglobin [Hgb]) < 75% will be excluded

- Congestive heart failure

- Clinically significant hypotension

- Symptoms of coronary artery disease

- Presence of cardiac arrhythmias on electrocardiograph (EKG) requiring drug therapy

- Ejection fraction < 50 % (echocardiogram or multi gated acquisition scan [MUGA])

- Symptomatic central nervous system metastases greater than 1 cm at time of therapy;
patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS)
metastases without significant edema may be considered for treatment

- Patients with active infections or oral temperature > 38.2 C within 72 hours of study
entry or systemic infection requiring chronic maintenance or suppressive therapy

- Chemotherapeutic agents (standard or experimental), radiation therapy, or other
immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with
bulky disease may undergo cytoreductive chemotherapy but treatment will be
discontinued at least 3 weeks prior to T cell therapy)

- Clinically significant autoimmune disorders or conditions of immunosuppression;
patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency
virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be
recently polymerase chain reaction (PCR)+ for hepatitis are not eligible for this
study; virology testing will be done within 6 months of T cell infusion; the severely
depressed immune system found in these infected patients and the possibility of
premature death would compromise study objectives

- Chemotherapeutic agents (standard or experimental), radiation therapy, or other
immunosuppressive therapies less than 3 weeks prior to T cell therapy

- Current treatment with steroids

- Patients must not be receiving any other experimental drugs within 3 weeks of the
initiation of the protocol and must have recovered from all side effects of such

- Patients for whom we are unable to generate MART-1 specific T cells
We found this trial at
1100 Fairview Avenue North
Seattle, Washington 98109
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium The Fred Hutchinson/University of Washington Cancer...
Seattle, WA
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