Therapeutic Autologous Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Metastatic Melanoma

This study has been terminated.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01106235
First received: April 8, 2010
Last updated: December 20, 2011
Last verified: December 2011
  Purpose

RATIONALE: Aldesleukin may stimulate lymphocytes to kill melanoma cells. Treating lymphocytes with interleukin-21 in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin in treating patients with metastatic melanoma


Condition Intervention Phase
Stage IV Melanoma
Biological: therapeutic autologous lymphocytes
Biological: aldesleukin
Drug: cyclophosphamide
Procedure: biopsy
Phase 1

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 IL-21 Modulated CD8+ Antigen-Specific T Cells 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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 [ Time Frame: 10 weeks post infusion ] [ Designated as safety issue: Yes ]
  • Functional and numeric in vivo persistence of adoptively transferred IL-21 modulated CTL and factors contributing to immunopotentiation in patients receiving IL-21 modulated CTL following cyclophosphamide conditioning [ Time Frame: 10 weeks post infusion ] [ Designated as safety issue: No ]
    Descriptive statistics (average, median standard deviation and student's t test) will be used to determine if an increase in the duration of in vivo persistence is observed using IL-21 modulated T cells when retrospectively compared with T cells generated under standard culture conditions (no IL-21 exposure in vitro).


Secondary Outcome Measures:
  • In vivo persistence and anti-tumor effect of the infused IL-21 modulated CTL [ Time Frame: 10 weeks post infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: April 2010
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (immunostimulant, autologous lymphocytes, and chemo)
Patients receive cyclophosphamide IV on days -3 and -2 followed by an infusion of IL-21 modulated, MART-1 specific CD8+ cytotoxic T lymphocytes over 30-60 minutes on day 0. Beginning within 24 hours of T cell infusion, patients receive low-dose aldesleukin SC BID for 14 days 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 SC
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Procedure: biopsy
Optional correlative studies
Other Name: biopsies

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the safety and toxicity of adoptively transferred interleukin (IL)-21 modulated cytotoxic T-lymphocyte (CTL) targeting a melanoma associated antigen in patients following cyclophosphamide conditioning.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred IL-21 modulated CTL and factors contributing to immunopotentiation in patients receiving IL-21 modulated CTL following cyclophosphamide conditioning.

SECONDARY OBJECTIVES:

I. Evaluate the antitumor effect of adoptively transferred IL-21 modulated CD8+ antigen-specific CTL following cyclophosphamide conditioning and post-infusion IL-2.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) on days -3 and -2 followed by an infusion of IL-21 modulated, melanoma antigen recognized by T cell (MART)-1 specific CD8+ cytotoxic T lymphocytes over 30-60 minutes on day 0. Beginning within 24 hours of T-cell infusion, patients receive low-dose aldesleukin subcutaneously (SC) twice daily (BID) for 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 8-10 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • FOR LEUKAPHERESIS:
  • Pulse > 45 or < 120
  • Weight >= 45 kg
  • Temperature =< 38 Celsius (C) (=< 100.4 Fahrenheit [F])
  • White blood cells (WBC) >= 3000
  • Hematocrit (HCT) >= 30%
  • Platelets >= 100,000
  • FOR T CELL INFUSION:
  • Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease
  • Tumor expression of MART-1 (2+ staining or > 25%) by immunohistochemistry (IHC)
  • Able to tolerate high-dose cyclophosphamide
  • Expression of human leukocyte antigen (HLA)-A2
  • Zubrod performance status of 0-1
  • Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan)
  • Normal cardiac stress test within 182 days prior to enrollment is required of all patients over 50 years old or those with an abnormal electrocardiogram (ECG), any history of cardiac disease, a family history of cardiac disease or hypertension

Exclusion Criteria:

  • Pregnant women, nursing mothers, men or women 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 > 1.6 mg/dL or creatinine clearance (CrCl) < 75 ml/min (calculated: Cockcroft and Gault equation: CrCl = (140 - age) x ideal body weight (IBW)/(serum creatinine [Scr] x 72) (x 0.85 for females)
  • Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3 x upper limit of normal
  • Direct bilirubin > 1.0 mg/dL
  • Prothrombin time > 1.5 x control (in the absence of systemic anticoagulation)
  • Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing at the discretion of their primary physician
  • 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 electrocardiogram (EKG) requiring drug therapy
  • Symptomatic central nervous system metastases greater than 1 cm at time of therapy; patients with 1-2 asymptomatic, less than 1cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then a repeat imaging will be performed if more than 3 weeks have elapsed from the last scan; patients will not be treated if CNS lesions are > 1 cm or if patient is symptomatic from brain metastasis
  • 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
  • Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell therapy)
  • Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be recently polymerase chain reaction positive (PCR+) for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives
  • Patients who, in the opinion of their physician, are not clinically suited for high-dose cytoxan
  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: NCT01106235

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: NCT01106235     History of Changes
Other Study ID Numbers: 2390.00, NCI-2010-00146
Study First Received: April 8, 2010
Last Updated: December 20, 2011
Health Authority: United States: Institutional Review Board

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 August 28, 2014