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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).

Studieoversigt

Detaljeret 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.

Undersøgelsestype

Interventionel

Tilmelding (Forventet)

33

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 120 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Maskning: Ingen (Åben etiket)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Overlevelse

Sekundære resultatmål

Resultatmål
Toksicitetsprofil
Klinisk tumorregression

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juni 2003

Primær færdiggørelse (Faktiske)

1. februar 2007

Studieafslutning (Faktiske)

1. september 2008

Datoer for studieregistrering

Først indsendt

5. juni 2003

Først indsendt, der opfyldte QC-kriterier

5. juni 2003

Først opslået (Skøn)

6. juni 2003

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

2. juli 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

30. juni 2017

Sidst verificeret

1. marts 2012

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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