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Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma

Tumor Infiltrating Lymphocytes (TIL Cells) Transduced With An Interleukin-2 (SBIL-2) Gene Following The Administration Of A Nonmyeloablative But Lymphocyte Depleting Regimen in Metastatic Melanoma

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and fludarabine use different ways to stop tumor cells from dividing so they stop growing or die. Inserting the gene for interleukin-2 into a person's tumor infiltrating lymphocytes may make the body build an immune response to kill tumor cells. Combining cyclophosphamide and fludarabine with gene-modified tumor cells may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of gene-modified tumor infiltrating lymphocytes when given together with cyclophosphamide and fludarabine and to see how well they work in patients with metastatic melanoma (phase I is closed to accrual 3/29/06).

Studieoversikt

Detaljert beskrivelse

OBJECTIVES:

Primary

  • Determine the survival of patients with metastatic melanoma administered interleukin-2 gene-modified tumor infiltrating lymphocytes after cyclophosphamide and fludarabine.
  • Compare survival results with prior Surgery Branch studies using adoptive cell therapy without the interleukin-2 retroviral vector (SBIL-2) gene.

Secondary

  • Determine clinical tumor regression in patients administered interleukin-2 gene-modified TIL after cyclophosphamide and fludarabine followed by interleukin-2.
  • Determine the toxicity profile of this regimen in these patients.

OUTLINE:

  • Phase I (closed to accrual as of 3/29/06):

    • Harvest: TIL are harvested, transduced with IL-2 gene, and expanded in vitro over a period of approximately 4 weeks.
    • Nonmyeloablative preparative regimen (chemotherapy): Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.
    • Lymphocyte administration: Patients receive IL-2 gene-transduced TIL IV over 20-30 minutes on day 0. They also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0 -5 (maximum 15 doses). Beginning 1-2 days after lymphocyte administration, patients receive filgrastim (G-CSF) subcutaneously (SC) daily, , until blood counts recover.
    • Retreatment: Patients are re-evaluated every 4-6 weeks. Retreatment depends on disease status after each regimen. Patients with dose-limiting toxicity do not receive further treatment.

      • No response: Patients with stable disease or disease progression after the initial treatment are followed or removed from the study.
      • Partial response: Patients with a partial or minor response after the initial treatment may receive retreatment, approximately 2-4 weeks later, with chemotherapy, IL-2 gene-transduced TIL, immunization, and high-dose IL-2 as above, every 4-6 weeks for up to 2 courses provided at least a partial response is documented after each regimen.
      • Complete response: Patients with a complete response receive no further treatment.
  • Phase II: Patients receive treatment and retreatment as in phase I with the MTD of IL-2 gene-transduced TIL.

Patients are followed every 3-6 weeks in the absence disease progression.

PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.

Studietype

Intervensjonell

Registrering (Forventet)

33

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • Maryland
      • Bethesda, Maryland, Forente stater, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
      • Bethesda, Maryland, Forente stater, 20892
        • NCI - Center for Cancer Research

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 120 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

  • Diagnosis of melanoma

    • Metastatic disease
    • Refractory to standard therapy including high-dose interleukin-2 (IL-2) therapy
  • Evaluable disease
  • Patients may enroll at the cell infusion stage provided they have tumor available for biopsy OR expandable SBIL-2-transduced tumor infiltrating lymphocytes available
  • Progressive disease during prior immunization to melanoma antigens or cellular therapy, with or without myeloablation, allowed
  • Symptomatic CNS lesions allowed provided immediate active treatment for symptomatic lesions has been completed

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count greater than 1,000/mm^3
  • WBC greater than 3,000/mm^3
  • Lymphocyte count greater than 500/mm^3
  • Platelet count greater than 100,000/mm^3
  • Hemoglobin greater than 8.0 g/dL
  • No coagulation disorder

Hepatic

  • Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL in patients with Gilbert's syndrome)
  • AST/ALT less than 3 times upper limit of normal
  • Hepatitis B surface antigen negative
  • Hepatitis C virus negative

Renal

  • Creatinine no greater than 1.6 mg/dL

Cardiovascular

  • No myocardial infarction
  • No cardiac arrhythmias
  • No abnormal stress thallium or comparable test
  • LVEF > 45% and normal stress cardiac test in patients with the following criteria:

    • 50 years old or greater
    • History of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias
  • No major cardiovascular illness

Pulmonary

  • No obstructive or restrictive pulmonary disease
  • No major respiratory illness
  • FEV_1 > 60% predicted in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction

Immunologic

  • HIV negative
  • No prior severe immediate hypersensitivity reaction
  • No primary or secondary immunodeficiency
  • No active systemic infection
  • No concurrent opportunistic infection
  • No major immune system illness

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 months after study therapy
  • Must sign a durable power of attorney

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • No prior anti-cytotoxic T-lymphocyte antibody-4 antibody (CTLA-4) allowed unless post-MDX010 treatment and colonoscopy with colonic biopsies are normal

Chemotherapy

  • Recovered from prior chemotherapy

Endocrine therapy

  • No concurrent steroids

Radiotherapy

  • Recovered from prior radiotherapy

Surgery

  • Not specified

Other

  • More than 4 weeks since prior systemic therapy

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Masking: Ingen (Open Label)

Hva måler studien?

Primære resultatmål

Resultatmål
Overlevelse

Sekundære resultatmål

Resultatmål
Giftighetsprofil
Klinisk tumorregresjon

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. juni 2003

Primær fullføring (Faktiske)

1. februar 2007

Studiet fullført (Faktiske)

1. september 2008

Datoer for studieregistrering

Først innsendt

5. juni 2003

Først innsendt som oppfylte QC-kriteriene

5. juni 2003

Først lagt ut (Anslag)

6. juni 2003

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

2. juli 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

30. juni 2017

Sist bekreftet

1. mars 2012

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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