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

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

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

Study Overview

• Status: Terminated
• Conditions: Recurrent Melanoma; Stage IV Melanoma; Stage III Melanoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Genetic: polymerase chain reaction; Biological: therapeutic autologous lymphocytes; Other: immunohistochemistry staining method; Biological: aldesleukin; Procedure: biopsy; Biological: denileukin diftitox

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (cellular adoptive immunotherapy); 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.

Other: laboratory biomarker analysis; Correlative studies; Genetic: polymerase chain reaction; Correlative studies; Other Names: PCR; Biological: therapeutic autologous lymphocytes; Given IV; Other Names: AL; Autologous Lymphocytes; autologous T cells; Other: immunohistochemistry staining method; Correlative studies; Other Names: immunohistochemistry; Biological: aldesleukin; Given SC; Other Names: Proleukin; IL-2; recombinant human interleukin-2; recombinant interleukin-2; Procedure: biopsy; Optional correlative studies; Other Names: biopsies; Biological: denileukin diftitox; Given IV; Other Names: DAB389 interleukin-2; DAB389 interleukin-2 immunotoxin; DAB389-IL2; DABIL2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sylvia Lee, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: July 23, 2009
• First Submitted That Met QC Criteria: July 23, 2009
• First Posted (Estimate): July 24, 2009

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Immunologic Factors; Aldesleukin; Interleukin-2; Immunotoxins; Denileukin diftitox
• Other Study ID Numbers: 2271.00; K12CA076930 (U.S. NIH Grant/Contract); NCI-2010-00738 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R21CA137647 (U.S. NIH Grant/Contract)