NCT00438984

Brief Summary

RATIONALE: Biological therapies, such as therapeutic autologous lymphocytes, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclophosphamide may also stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor cells. Giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin may be an effective treatment for melanoma. PURPOSE: This phase I trial is studying the side effects of giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin in treating patients with stage IV melanoma

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
11

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2006

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2006

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

February 20, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 22, 2007

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2011

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2012

Completed
Last Updated

March 16, 2012

Status Verified

March 1, 2012

Enrollment Period

4.1 years

First QC Date

February 20, 2007

Last Update Submit

March 14, 2012

Conditions

Recurrent MelanomaStage IV Melanoma

Outcome Measures

Primary Outcomes (2)

  • The identification of a CY/IL-2 regimen that is considered to be safe

    Baseline, 4 weeks and 8 weeks

  • The identification of a CY/IL-2 regimen (among those considered safe) which yields the greatest effect on the duration of in vivo persistence of adoptively transferred CTL clones

    Baseline, 4 weeks and 8 weeks

Study Arms (1)

Treatment (chemotherapy, immunosuppressive, lymphocytes)

EXPERIMENTAL

All patients receive high-dose cyclophosphamide IV on days -3 and -2 and autologous antigen-specific cytotoxic CD8+ T-lymphocyte clones IV over 30-60 minutes on day 0. COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin SC twice daily on days 0-14. COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose aldesleukin IV 3 times daily on days 0-5.

Drug: cyclophosphamideBiological: therapeutic autologous lymphocytesBiological: aldesleukinOther: immunohistochemistry staining methodProcedure: biopsyOther: laboratory biomarker analysisOther: immunologic techniqueGenetic: polymerase chain reaction

Interventions

cyclophosphamideDRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (chemotherapy, immunosuppressive, lymphocytes)
therapeutic autologous lymphocytesBIOLOGICAL

Given IV

Also known as: AL, Autologous Lymphocytes, autologous T cells
Treatment (chemotherapy, immunosuppressive, lymphocytes)
aldesleukinBIOLOGICAL

Given IV or SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Treatment (chemotherapy, immunosuppressive, lymphocytes)
immunohistochemistry staining methodOTHER

Correlative studies

Also known as: immunohistochemistry
Treatment (chemotherapy, immunosuppressive, lymphocytes)
biopsyPROCEDURE

Optional correlative studies

Also known as: biopsies
Treatment (chemotherapy, immunosuppressive, lymphocytes)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (chemotherapy, immunosuppressive, lymphocytes)
immunologic techniqueOTHER

Correlative studies

Also known as: immunological laboratory methods, laboratory methods, immunological
Treatment (chemotherapy, immunosuppressive, lymphocytes)
polymerase chain reactionGENETIC

Correlative studies

Also known as: PCR
Treatment (chemotherapy, immunosuppressive, lymphocytes)

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease
  • Expression of HLA-A2, B44, or A3 as determined by Fred Hutchinson Cancer Research Center (FHCRC) human leukocyte antigen (HLA) typing lab
  • Zubrod performance status of 0-1
  • Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, 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, hypercholesterolemia or hypertension
  • FOR LEUKAPHERESIS:
  • Pulse \> 45 or \< 120
  • Weight \>= 45 kg
  • White blood cell count (WBC) \>= 3,000
  • Temperature =\< 38C (=\< 100.4 F)
  • Hematocrit (HCT) \>= 30%
  • Platelets \>= 100,000
  • FOR T CELL INFUSION: Patients must be willing and able to discontinue the use of all anti-hypertensive medications 24 hours prior to and during IL-2 therapy

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 \< 75 ml/min
  • Serum glutamic oxaloacetic transaminase (SGOT) \> 150 IU or \> 3x upper limit of normal
  • Bilirubin \> 1.6 mg/dL
  • Prothrombin time \> 1.5 x control
  • 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) \< 2.0 L or carbon monoxide diffusing capacity (DLco) (corr for Hgb) \< 75% will be excluded
  • 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 electrocardiograph (EKG) requiring drug therapy;
  • Ejection fraction \< 50 % (echocardiogram or multi gated acquisition scan \[MUGA\])
  • Symptomatic central nervous system metastases greater than 1 cm at the time of therapy; patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, than 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)
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

CyclophosphamidealdesleukinInterleukin-2ImmunohistochemistryBiopsyImmunologic TechniquesPolymerase Chain Reaction

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsInterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological FactorsHistocytochemistryCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHistological TechniquesInvestigative TechniquesCytodiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalSurgical Procedures, OperativeNucleic Acid Amplification TechniquesGenetic 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

February 20, 2007

First Posted

February 22, 2007

Study Start

December 1, 2006

Primary Completion

January 1, 2011

Study Completion

February 1, 2012

Last Updated

March 16, 2012

Record last verified: 2012-03

Locations

US(1)