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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Recurrent Melanoma, Stage IV Melanoma

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment-related dose limiting toxicity (DLT) as defined by Grade 3 or greater unexpected toxicity by the NCI Common Toxicity Criteria (CTC) v4.0

Outcome Description:

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%.

Outcome Time Frame:

Up to 8 weeks after the T cell infusion

Safety Issue:

Yes

Principal Investigator

Sylvia Lee

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2481.00

NCT ID:

NCT01339663

Start Date:

March 2012

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Stage IV Melanoma
  • Melanoma

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109