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Phase I Study To Evaluate Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Cyclophosphamide Conditioning For Patients With Metastatic Melanoma


Phase 1
18 Years
75 Years
Not Enrolling
Both
Recurrent Melanoma, Stage IV Melanoma

Thank you

Trial Information

Phase I Study To Evaluate Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Cyclophosphamide Conditioning For Patients With Metastatic Melanoma


PRIMARY OBJECTIVES:

I. To assess the safety and toxicity of cellular adoptive immunotherapy in melanoma patients
receiving autologous CD8+ antigen-specific T cell clones following cyclophosphamide
conditioning and post-infusion IL-2.

II. To assess the duration of in vivo persistence of adoptively transferred CD8+ T cell
clones.

SECONDARY OBJECTIVES:

I. Evaluate the antitumor effect of adoptively transferred CD8+ antigenspecific cytotoxic t
lymphocytes (CTL) clones following cyclophosphamide conditioning and post-infusion IL-2.

OUTLINE:

Patients are assigned 1of 2 treatment cohorts.

All patients receive high-dose cyclophosphamide intravenously (IV) on days -3 and -2 and
autologous antigen-specific cytotoxic CD8+ T lymphocyte clones IV over 30-60 minutes on day
0.

COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin
subcutaneously (SC) twice daily on days 0-14.

COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose
aldesleukin IV 3 times daily on days 0-5.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, and every
3 months thereafter for up to 1 year.


Inclusion Criteria:



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

- Expression of HLA-A2, B44, or A3 as determined by Fred Hutchinson Cancer Research
Center (FHCRC) human leukocyte antigen (HLA) typing lab

- Zubrod performance status of 0-1

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

- Normal cardiac stress test within 182 days prior to enrollment is required of all
patients over 50 years old or those with an abnormal electrocardiogram (ECG), any
history of cardiac disease, a family history of cardiac disease, hypercholesterolemia
or hypertension

- FOR LEUKAPHERESIS:

- Pulse > 45 or < 120

- Weight >= 45 kg

- White blood cell count (WBC) >= 3,000

- Temperature =< 38C (=< 100.4 F)

- Hematocrit (HCT) >= 30%

- Platelets >= 100,000

- FOR T CELL INFUSION: Patients must be willing and able to discontinue the use of all
anti-hypertensive medications 24 hours prior to and during IL-2 therapy

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 Hgb) < 75% will be excluded

- Significant cardiovascular abnormalities as defined by any one of the following:

- 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 the 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; if
sub-centimeter CNS lesions are noted at study entry, than a repeat imaging will be
performed if more than 3 weeks have elapsed from the last scan; patients will not be
treated if CNS lesions are > 1 cm or if patient is symptomatic from brain metastasis

- 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

- FOR T CELL INFUSION: 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

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

- FOR T CELL INFUSION: Current treatment with steroids

- FOR T CELL INFUSION: 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The identification of a CY/IL-2 regimen that is considered to be safe

Outcome Time Frame:

Baseline, 4 weeks and 8 weeks

Safety Issue:

Yes

Principal Investigator

Cassian Yee

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:

2140.00

NCT ID:

NCT00438984

Start Date:

December 2006

Completion Date:

February 2012

Related Keywords:

  • Recurrent Melanoma
  • Stage IV Melanoma
  • Melanoma

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109