- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT00062036
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).
Tutkimuksen yleiskatsaus
Tila
Ehdot
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Odotettu)
Vaihe
- Vaihe 2
- Vaihe 1
Yhteystiedot ja paikat
Opiskelupaikat
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Maryland
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Bethesda, Maryland, Yhdysvallat, 20892-1182
- Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
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Bethesda, Maryland, Yhdysvallat, 20892
- NCI - Center for Cancer Research
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Naamiointi: Ei mitään (avoin tarra)
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
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Eloonjääminen
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
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Myrkyllisyysprofiili
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Kliininen kasvaimen regressio
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Yhteistyökumppanit ja tutkijat
Yhteistyökumppanit
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Neoplasmat histologisen tyypin mukaan
- Neoplasmat
- Neuroektodermaaliset kasvaimet
- Neoplasmat, sukusolut ja alkiot
- Kasvaimet, hermokudos
- Neuroendokriiniset kasvaimet
- Nevi ja melanoomat
- Melanooma
- Huumeiden fysiologiset vaikutukset
- Farmakologisen vaikutuksen molekyylimekanismit
- Infektiota estävät aineet
- Ääreishermoston aineet
- Viruksenvastaiset aineet
- HIV-vastaiset aineet
- Antiretroviraaliset aineet
- Analgeetit
- Aistijärjestelmän agentit
- Analgeetit, ei-huumeet
- Reumaattiset aineet
- Antimetaboliitit, antineoplastiset
- Antimetaboliitit
- Antineoplastiset aineet
- Immunosuppressiiviset aineet
- Immunologiset tekijät
- Antineoplastiset aineet, alkyloiva
- Alkylointiaineet
- Myeloablatiiviset agonistit
- Adjuvantit, immunologiset
- Aldesleukin
- Syklofosfamidi
- Fludarabiini
- Fludarabiinifosfaatti
- Interleukiini-2
- Freundin adjuvantti
Muut tutkimustunnusnumerot
- 030162
- 03-C-0162
- NCI-5855
- CDR0000304438
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