Therapeutic Autologous Lymphocytes, Aldesleukin, and Denileukin Diftitox in Treating Patients With Stage III-IV Melanoma

NCT00945269 | Terminated Phase 1 DMC

• 4 other identifiers: 2271.00NCI-2010-00738K12CA076930R21CA137647
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: White blood cells that have been treated in a laboratory may be able to kill tumor cells in patients with melanoma. Aldesleukin and denileukin diftitox may stimulate the white blood cells to kill melanoma cells. Giving therapeutic autologous lymphocyte therapy together with aldesleukin and denileukin diftitox may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects of giving therapeutic autologous lymphocytes together with aldesleukin and denileukin diftitox and to see how well it works in treating patients with stage III-IV melanoma

Conditions

Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• In vivo survival of CD8+ transferred T-clones

  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.

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

Study Arms (1)

Treatment (cellular adoptive immunotherapy)

EXPERIMENTAL

Patients receive autologous T-cell IV over 30-60 minutes on days 0 and 28 and low-dose aldesleukin 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.

Biological: therapeutic autologous lymphocytes; Biological: aldesleukin; Biological: denileukin diftitox; Procedure: biopsy; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Genetic: polymerase chain reaction

Interventions

therapeutic autologous lymphocytes BIOLOGICAL

Given IV

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

Treatment (cellular adoptive immunotherapy)

aldesleukin BIOLOGICAL

Given SC

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

Treatment (cellular adoptive immunotherapy)

denileukin diftitox BIOLOGICAL

Given IV

Also known as: DAB389 interleukin-2, DAB389 interleukin-2 immunotoxin, DAB389-IL2, DABIL2

Treatment (cellular adoptive immunotherapy)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (cellular adoptive immunotherapy)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment (cellular adoptive immunotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (cellular adoptive immunotherapy)

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Treatment (cellular adoptive immunotherapy)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

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; denileukin diftitox; Biopsy; Immunohistochemistry; 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)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; 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; Nucleic Acid Amplification Techniques; Genetic Techniques

Study Officials

• Sylvia Lee

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: July 24, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: November 15, 2022

Record last verified: 2022-11

Locations

US (1)