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

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Stage IV Melanoma

Intervention: therapeutic autologous lymphocytes (Biological); aldesleukin (Biological); cyclophosphamide (Drug); biopsy (Procedure)

Phase: Phase 1

Status: Terminated

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Cassian Yee, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


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

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Safety and toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0

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 outcome: In vivo persistence and anti-tumor effect of the infused IL-21 modulated CTL

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.


Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.


Inclusion Criteria:


- 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


- 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


- 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

Locations and Contacts

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

Starting date: April 2010
Last updated: December 20, 2011

Page last updated: August 23, 2015

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