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

This study has been completed.
Sponsor:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00553306
First received: November 2, 2007
Last updated: April 21, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Recurrent Melanoma
Stage IV Melanoma
Biological: therapeutic autologous lymphocytes
Biological: aldesleukin
Drug: cyclophosphamide
Procedure: biopsy
Other: immunohistochemistry staining method
Other: flow cytometry
Genetic: polymerase chain reaction
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study To Evaluate Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Cyclophosphamide Conditioning For Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Safety and toxicity as assessed by NCI CTC version 3.0 [ Time Frame: 8 weeks post treatment ] [ Designated as safety issue: Yes ]
  • Antitumor effects of CD4+ and CD8+ antigen-specific T-cells [ Time Frame: 8 weeks post treatment ] [ Designated as safety issue: No ]
  • Duration of in vivo persistence of adoptively transferred CD8+ antigen-specific T cell clones in the presence or absence of transferred CD4+ T cells [ Time Frame: 8 weeks post treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • In vivo antitumor efficacy of the infused autologous antigen-specific CD4+ T cells [ Time Frame: 8 weeks post treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 6
Study Start Date: September 2007
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: therapeutic autologous lymphocytes
Given IV
Other Names:
  • AL
  • Autologous Lymphocytes
  • autologous T cells
Biological: aldesleukin
Given subcutaneously
Other Names:
  • IL-2
  • interleukin II
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
  • TCGF, interleukin
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Enduxan
Procedure: biopsy
Optional correlative studies
Other Name: biopsies
Other: immunohistochemistry staining method
Optional correlative studies
Other Name: immunohistochemistry
Other: flow cytometry
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00553306

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Cassian Yee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Yee, Cassian, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT00553306     History of Changes
Other Study ID Numbers: 2179.00, NCI-2010-01281
Study First Received: November 2, 2007
Last Updated: April 21, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Aldesleukin
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on July 29, 2014