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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/Phase 2
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
using autologous CD4+ and CD8+ antigen-specific T cell clones.

II. To evaluate the antitumor effects of CD4+ and CD8+ antigen-specific T cells in patients
with metastatic melanoma.

III. To determine the duration of in vivo persistence of adoptively transferred CD8+
antigen-specific T cell clones in the presence or absence of transferred CD4+ T cells.

SECONDARY OBJECTIVES:

I. To assess the in vivo antitumor efficacy of the infused autologous antigen-specific CD4+
T cells.

OUTLINE: This is a phase I study followed by a phase II study.

Beginning 48 hours before T-cell infusion, patients receive cyclophosphamide IV. Patients
then receive antigen-specific CD8+ T cells IV alone or with CD4+ T helper clones over 1-2
hours on day 0. Patients also receive aldesleukin subcutaneously twice daily on days 0-13.
Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up weekly for 8 weeks, and then
periodically thereafter.

Inclusion Criteria


Inclusion

- Histopathologically documented metastatic melanoma

- Karnofsky Performance status of at least 70%

- Expected survival of greater than 16 weeks

- WBC > 2,500/uL (ANC > 1,000 uL)

- Platelet count > 80,000 uL

- HCT > 28%

- Patients whose tumor expresses targeted antigen and restricting allele against which
CD4 and CD8 T cell clones can be generated

- No CNS metastasis

- Patient's whose tumor expresses an antigen and HLA type for which both an HLA Class I
and HLA Class II epitope are listed, will be eligible for this study

- CD4 and CD8 T cell clones do not necessarily have to target the same antigen to be
eligible for the study, it is only necessary that the targeted antigen is expressed
by the tumor and its epitope is restricted by an HLA allele expressed by the patient

- Evidence of measurable residual disease by clinical exam or imaging studies

Exclusion

- Current central nervous system metastases; patients with history of CNS metastases
that show no current evidence of active disease are eligible

- 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

- Current treatment with steroids

- Patients who are HIV seropositive (poor CD4 T cell generation due to low CD4 T cell
recovery and likely HIV reservoir in stimulator cells used in vitro culture)

- Prognosis less than 6 months

- FOR T CELL INFUSION:

- Pregnant women, nursing mothers 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 > 2.0 mg/dL

- Significant hepatic dysfunction (hepatic toxicity >= grade 2 (NCICTC) of whatever
origin

- Clinically significant pulmonary dysfunction, as determined by medical history and
physical exam; patients so identified will undergo pulmonary functions testing and
those with FEV1 < 60% of normal or DLco (corr for Hgb) < 55% 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 EKG requiring drug therapy

- Ejection fraction < 50% excludes patients

- Current central nervous system metastases; patients with history of CNS metastases
that show no current evidence of active disease are eligible

- Serum calcium > 12 mg/dL

- Chemotherapeutic agents (standard or experimental), radiation therapy, or other
immunosuppressive therapies less than 4 weeks prior to T cell therapy; patients with
bulky disease may undergo 1-2 courses of cytoreductive chemotherapy but treatment
will be discontinued at least 4 weeks prior to T cell therapy; patients should have
recovered fully from all previous treatment-related toxicities

- History of seizures

- Patients must not be receiving any other experimental drugs within 4 weeks of the
initiation of the protocol and must have recovered from all side effects of such
therapy

- Patients with >= Grade 2 hepatotoxicity are excluded

- Patients with a history of autoimmune disease requiring active systemic therapy are
excluded

- The following agents are not allowed while on study: systemic corticosteroids (except
as outlined for management of toxicity of nontransduced CTL), immunotherapy (for
example, interleukins, interferons, melanoma vaccines, intravenous immunoglobulin,
expanded polyclonal TIL or LAK therapy), pentoxifylline, or other investigational
agents

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Safety and toxicity as assessed by NCI CTC version 3.0

Outcome Time Frame:

8 weeks post treatment

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:

2179.00

NCT ID:

NCT00553306

Start Date:

September 2007

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Stage IV Melanoma
  • Melanoma

Name

Location

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