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

NCT00553306 | Completed Phase 1 DMC

• 2 other identifiers: 2179.00NCI-2010-01281
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (3)

• Safety and toxicity as assessed by NCI CTC version 3.0

  8 weeks post treatment

• Antitumor effects of CD4+ and CD8+ antigen-specific T-cells

  8 weeks post treatment

• Duration of in vivo persistence of adoptively transferred CD8+ antigen-specific T cell clones in the presence or absence of transferred CD4+ T cells

  8 weeks post treatment

Secondary Outcomes (1)

• In vivo antitumor efficacy of the infused autologous antigen-specific CD4+ T cells

  8 weeks post treatment

Study Arms (1)

Arm I

EXPERIMENTAL

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; Biological: aldesleukin; Drug: cyclophosphamide; Procedure: biopsy; Other: immunohistochemistry staining method; Other: flow cytometry; Genetic: polymerase chain reaction

Interventions

therapeutic autologous lymphocytes BIOLOGICAL

Given IV

Also known as: AL, Autologous Lymphocytes, autologous T cells

Arm I

aldesleukin BIOLOGICAL

Given subcutaneously

Also known as: IL-2, interleukin II, Proleukin, recombinant human interleukin-2, recombinant interleukin-2, TCGF, interleukin

Arm I

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

Arm I

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Arm I

immunohistochemistry staining method OTHER

Optional correlative studies

Also known as: immunohistochemistry

Arm I

flow cytometry OTHER

Correlative studies

Arm I

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Arm I

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Interleukin-2; Interleukins; Cyclophosphamide; Biopsy; Immunohistochemistry; Flow Cytometry; Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Nucleic Acid Amplification Techniques; Genetic Techniques

Study Officials

• Cassian Yee

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2007
• First Posted: November 5, 2007
• Study Start: September 1, 2007
• Primary Completion: August 1, 2010
• Study Completion: March 1, 2012
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (1)