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

NCT01106235 | Terminated Phase 1 DMC

• 2 other identifiers: 2390.00NCI-2010-00146
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Stage IV Melanoma

Outcome Measures

Primary Outcomes (2)

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

  10 weeks post infusion

• 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

  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).

  10 weeks post infusion

Secondary Outcomes (1)

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

  10 weeks post infusion

Study Arms (1)

Treatment (immunostimulant, autologous lymphocytes, and chemo)

EXPERIMENTAL

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; Biological: aldesleukin; Drug: cyclophosphamide; Procedure: biopsy

Interventions

therapeutic autologous lymphocytes BIOLOGICAL

Given IV

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

Treatment (immunostimulant, autologous lymphocytes, and chemo)

aldesleukin BIOLOGICAL

Given SC

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

Treatment (immunostimulant, autologous lymphocytes, and chemo)

cyclophosphamide DRUG

Given IV

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

Treatment (immunostimulant, autologous lymphocytes, and chemo)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (immunostimulant, autologous lymphocytes, and chemo)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

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; Cyclophosphamide; Biopsy

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; 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

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 8, 2010
• First Posted: April 19, 2010
• Study Start: April 1, 2010
• Primary Completion: November 1, 2011
• Last Updated: December 21, 2011

Record last verified: 2011-12

Locations

US (1)