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Phase I/II Study To Evaluate The Safety Of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following CD25 Lymphodepletion For Patients With Metastatic Melanoma


Phase 1/Phase 2
18 Years
75 Years
Not Enrolling
Both
Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma

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Trial Information

Phase I/II Study To Evaluate The Safety Of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following CD25 Lymphodepletion For Patients With Metastatic Melanoma


PRIMARY OBJECTIVES:

I. Assess the safety of cellular adoptive immunotherapy in melanoma patients using
autologous CD8+ antigen-specific T-cell clones following CD25 lymphodepletion.

II. Determine the influence of CD25 lymphodepletion on the duration of in vivo persistence
of adoptively transferred CD8+ antigen-specific cytotoxic T-cell (CTL) clones.

SECONDARY OBJECTIVES:

I. Assess the anti-tumor efficacy of cellular adoptive immunotherapy in melanoma patients
using autologous CD8+ antigen-specific T cell clones following CD25 lymphodepletion.

II. Evaluate the induction of T cells to non-targeted tumor-associated antigens
(antigen-spreading) following adoptive transfer of CD8+ antigen-specific CTL and CD25
lymphodepletion.

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

Patients receive autologous T-cell intravenously (IV) over 30-60 minutes on days 0 and 28
and low-dose aldesleukin subcutaneously (SC) twice daily on days 0 to 13 and 28 to 41.
Beginning 4-6 days before second T- cell infusion, patients receive denileukin diftitox IV
over 30 minutes on days 1-3. 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 then
every 3 months thereafter.


Inclusion Criteria:



- Histopathological documentation of melanoma

- Expression of human leukocyte antigen (HLA)-A2 or B44 as determined by HLA typing lab

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

- Karnofsky Performance status of at least 80% and an expected survival of greater than
6 months

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

- Normal cardiac stress test (treadmill, echocardiogram, or myocardial perfusion scan)
within 182 days prior to enrollment is required of patients with a history of cardiac
disease

- Pulse > 45 or < 120

- Weight >= 45 kg

- Temperature =< 38C (< 100.4 F)

- White blood cells (WBC) >= 3,000

- Hematocrit (HCT) >= 30%

- Platelets >= 100,000

- Patients must be willing and able to discontinue the use of all antihypertensive
medications 24 hours prior to and during IL2 therapy

Exclusion Criteria:

- Pregnant women, nursing mothers, or women of reproductive ability who are unwilling
to use effective contraception or abstinence

- Serum creatinine > 1.6mg/dL

- Creatinine clearance < 75 ml/min

- Aspartate aminotransferase (AST) > 2.5 x upper limit of normal

- Alanine aminotransferase (ALT) > 2.5 x upper limit of normal

- Bilirubin > 1.6 or international normalized ratio (INR) > 1.5 due to hepatic
dysfunction

- Albumin < 3.0g/dL

- 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) < 80% predicted or diffusing
capacity of the lung for carbon monoxide (DLco) (corr for hemoglobin [Hgb]) < 75%
will be excluded

- Significant cardiovascular abnormalities as defined by any one of the following:
congestive heart failure, symptoms of coronary artery disease

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

- Patients with active infections or oral temperature > 38.2 C within 48 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)

- Concurrent 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

- 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:

In vivo survival of CD8+ transferred T-clones

Outcome Description:

The design of this trial using the first infusion of CD8 T cells administered alone as a baseline for each patient permits intra-patient analysis using paired samples with increased statistical power.

Outcome Time Frame:

Days +0, 1, 3, 7, 14, 22, 28, 29, 31, 35, 42, 49, 56, 63, 70, 77, 84

Safety Issue:

No

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:

2271.00

NCT ID:

NCT00945269

Start Date:

July 2009

Completion Date:

January 2011

Related Keywords:

  • Recurrent Melanoma
  • Stage III Melanoma
  • Stage IV Melanoma
  • Melanoma

Name

Location

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