Laboratory-Treated T Cells and Aldesleukin After Cyclophosphamide in Treating Patients With Stage IV Melanoma

NCT ID: NCT00553306

Last Updated: 2017-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2012-03-31

Brief Summary

RATIONALE: Laboratory-treated T cells may be able to kill tumor cells when they are put back into the body. Aldesleukin and cyclophosphamide may stimulate the immune system in different ways and stop tumor cells from growing. Giving laboratory-treated T cells together with aldesleukin after cyclophosphamide may be an effective treatment for melanoma.

PURPOSE: This phase I/II trial is studying the side effects of giving laboratory-treated T cells together with aldesleukin after cyclophosphamide and to see how well they work in treating patients with stage IV melanoma.

Detailed Description

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.

Conditions

Recurrent Melanoma; Stage IV Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

therapeutic autologous lymphocytes

Intervention Type: BIOLOGICAL

Given IV

aldesleukin

Intervention Type: BIOLOGICAL

Given subcutaneously

cyclophosphamide

Intervention Type: DRUG

Given IV

biopsy

Intervention Type: PROCEDURE

Optional correlative studies

immunohistochemistry staining method

Intervention Type: OTHER

Optional correlative studies

flow cytometry

Intervention Type: OTHER

Correlative studies

polymerase chain reaction

Intervention Type: GENETIC

Correlative studies

Interventions

therapeutic autologous lymphocytes

Given IV

Intervention Type: BIOLOGICAL

aldesleukin

Given subcutaneously

Intervention Type: BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type: DRUG

biopsy

Optional correlative studies

Intervention Type: PROCEDURE

immunohistochemistry staining method

Optional correlative studies

Intervention Type: OTHER

flow cytometry

Correlative studies

Intervention Type: OTHER

polymerase chain reaction

Correlative studies

Intervention Type: GENETIC

Other Intervention Names

AL; Autologous Lymphocytes; autologous T cells; IL-2; interleukin II; Proleukin; recombinant human interleukin-2; recombinant interleukin-2; TCGF, interleukin; CPM; CTX; Cytoxan; Endoxan; Endoxana; Enduxan; biopsies; immunohistochemistry; PCR

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cassian Yee

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Other Identifiers

NCI-2010-01281

Identifier Type: -

Identifier Source: secondary_id

2179.00

Identifier Type: -

Identifier Source: org_study_id