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

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 -4 and -3 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.

• cyclophosphamide (Drug), also known as CPM, CTX, Cytoxan, Endoxan, Endoxana: Given IV
• aldesleukin (Biological), also known as IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2: Given SC
• autologous tumor cell vaccine (Biological), also known as AC vaccine, ATCV, Autologous Cell Vaccine: Receive T-APC via IV
• laboratory biomarker analysis (Other): Correlative studies
• immunologic technique (Other), also known as immunological laboratory methods, laboratory methods, immunological: Correlative studies
• immunohistochemistry staining method (Other), also known as immunohistochemistry: Correlative studies
• polymerase chain reaction (Genetic), also known as PCR: Correlative studies
• therapeutic autologous lymphocytes (Biological), also known as AL, Autologous Lymphocytes, autologous T cells: Receive adoptively transferred CD8+ antigen-specific T cell clones via IV

Primary outcomes

• Treatment-related dose limiting toxicity (DLT) as defined by Grade 3 or greater unexpected toxicity by the NCI Common Toxicity Criteria (CTC) v4.0 [Up to 8 weeks after the T cell infusion]: Assessed at the maximum tolerated dose (MTD) or dose level immediately below the dose level for which the incidence of DLT was less than 35%.
• In vivo persistence of adoptively transferred T cells [At 4 weeks]: Assessed by intrapatient comparison between the first (without T-APC) and second (with T-APC) CTL infusion. Descriptive statistics will be applied and t-tests of intrapatient in vivo T cell persistence between the two Infusions will be determined.

Secondary outcomes

• Clinical response [Up to 8 weeks after second dose]

Sex: All, ages: 18 Years to any

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 therapy
* Patients for whom we are unable to generate MART-1 specific T cells

• Sylvia Lee, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

NIH grants: K12CA076930