- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT00923390
Phase 1/2 Study of Metastatic Renal Cancer Using T-Cells Transduced With a T-Cell Receptor Which Recognizes TRAIL Bound to the DR4 Receptor
6. dubna 2019 aktualizováno: National Cancer Institute (NCI)
Background:
- An experimental cancer treatment procedure involves taking a patient s own tumor or blood cells, modifying them with a gene that targets proteins on the surface of tumor cells, and growing those cells in a laboratory. The modified cells are then given back to the patient by intravenous (IV) transfusion, in the hope that the new cells will attack and destroy the cancer cells without harming healthy tissue.
- This procedure has been used for melanoma patients, and researchers are now attempting to use this treatment for patients with renal (kidney) cancer. In the laboratory, this attack kills nearly all kidney cancers tested, but not normal tissues. However, the effectiveness and possible side effects of this treatment are still being studied.
Objectives:
- To find out if cells modified to target DR4 and TRAIL (two proteins found on the surface of many kidney tumors) are effective in treating kidney cancer.
- To determine the maximum tolerated dose (the highest dose that does not cause unacceptable side effects) of the modified cells.
Eligibility:
- Patients 18 years of age and older with metastatic renal cancer whose disease has not responded to standard treatment.
- Patients will be divided into two study branches: Arm A for those who will be receiving modified cells from their biopsied tumor, and Arm B for those who will be receiving their own modified white blood cells.
Design:
- Five-stage treatment process, outpatient for stages 1 and 5 and inpatient for stages 2 through 4:
- Work-up (1 to 2 weeks): Physical examination, heart and lung function tests, imaging tests, blood and/or tumor samples taken.
- IV chemotherapy (1 week): Cyclophosphamide and fludarabine to prepare for the new cell infusion.
- IV cell infusion and treatment with IL-2 to support the modified cells (4 days).
- Recovery (1 to 2 weeks): Recover from effects of chemotherapy and infusion.
- Follow-up (every 1 to 6 months): Return to clinic for physical exam, review of side effects, other tests.
- Follow-up evaluations will continue to determine the success of the treatment.
- Evaluations during the treatment period:
- Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
- Blood and urine tests.
- Disease evaluation and monitoring on both inpatient and outpatient basis.
- Because researchers do not know the long-term side effects of gene therapy, patients will be asked to participate in long-term follow up for up to 15 years. The follow-up will involve yearly physical exams and medical history, and blood collection (3, 6 and 12 months after treatment, and every year after that).
Přehled studie
Postavení
Ukončeno
Podmínky
Detailní popis
Background:
- The clinical administration of tumor-reactive T-cells grown in vitro is a highly active therapy for patients with metastatic melanoma in experimental protocols when they are combined with preparative lymphodepleting chemotherapy and systemic IL-2.
- We cloned a novel T-cell from the blood of a patient with renal cell cancer (RCC), which recognizes nearly all human renal cancer lines irrespective of MHC haplotype.
- The alpha sign and beta sign chain of T-cell receptor from this clone, 2G-1, can be introduced into human lymphocytes by retroviral transduction and confers this same recognition of RCC.
- This TCR was found to recognize TNF-related apoptosis inducing ligand (TRAIL) bound to its receptor DR4.
- Both TRAIL and agonist antibodies to DR4 have tumor specificity and are in current clinical trials for cancer.
- Two amino acid modifications of the native TCR greatly augmented its recognition of RCCs without altering background reactivity.
Objectives:
Primary:
- Determine if the administration of T-cells retrovirally transduced with the 2G-1 TCR, with preparative chemotherapy and IL-2, can cause the regression of metastatic RCC.
- To identify the maximum tolerated dose (MTD) for cells incorporating a TCR in PBL and in TIL.
Secondary:
- Determine the toxicities of these T-cells administered in the above fashion.
- Determine TCR and vector presence in the post treatment phase.
Eligibility:
- Patients with measurable metastatic clear cell renal cancer who have previously received at least one systemic standard care regimen and have progressed or be found to be intolerant of standard therapies.
- Patients must be eligible for high-dose IL-2.
- Patients must not have active or clinically symptomatic CNS metastases within the previous 3 months.
- Patients must have acceptable hematopoietic and major organ function as determined by laboratory and/or functional testing.
Design:
- A phase I-II dose escalating protocol with 2 arms. Patients in Arm A will receive peripheral blood lymphocytes transduced with the 2G-1 TCR; patients in Arm B will receive renal TIL transduced with the 2G-1 TCR. Arm B will begin after a safe dose has been defined in Arm A.
- Once MTD has been established for each arm, up to 24 patients will be enrolled in each arm of the phase II stage.
- Patients will receive a nonmyeloablative but lymphocyte-depleting preparative regimen consisting of cyclophosphamide and fludarabine followed in one to four days by IV infusion of their transduced cells and subsequent IV aldesleukin administration.
- Up to 106 patients may be enrolled over 3-4 years.
Typ studie
Intervenční
Zápis (Aktuální)
5
Fáze
- Fáze 1
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Maryland
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Bethesda, Maryland, Spojené státy, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let až 99 let (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
INCLUSION CRITERIA:
- Measurable metastatic clear cell renal cancer. Histologic diagnosis will be confirmed by the Laboratory of Pathology at the NCI.
- Patients must have previously received at least one systemic standard care regimens and have progressed or be found to be intolerant of standard therapies.
- Greater than or equal to 18 years of age.
- Willing to sign a durable power of attorney
- Able to understand and sign the Informed Consent Document
- Clinical performance status of ECOG 0 or 1.
- Life expectancy of greater than three months.
- Patients of both genders must be willing to practice birth control during and for four months after receiving the preparative regimen.
Serology:
- Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immunecompetence, and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
Hematology:
- Absolute neutrophil count greater than or equal to 1000/mm3 without the support of filgrastim.
- WBC greater than or equal to 3000/mm3.
- Platelet count greater than or equal to 100,000/mm3.
- Hemoglobin greater than or equal to 8.0 g/dl.
Chemistry:
- Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
- Serum creatinine less than or equal to 1.6 mg/dl.
- Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for alopecia or skin rash, which must have recovered to a grade 2 or less).
- Patients who have previously received anti-CTLA4 antibody must have a normal colonoscopy with normal colonic biopsies.
EXCLUSION CRITERIA:
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- Active systemic infections; coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; myocardial infarction; cardiac arrhythmias; obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
- Concurrent systemic steroid therapy
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- History of coronary revascularization or ischemic symptoms
Documented LVEF less than or equal to 45%. LVEF will be evaluated in patients with:
- History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
- Age greater than or equal to 60 years old
Documented FEV1 less than or equal to 60% predicted. Screening pulmonary function testing will be done in patients with:
- A prolonged history of cigarette smoking (20 pk/year of smoking, who have not quit within the past 2 years).
- Symptoms of respiratory dysfunction
- Patients who have a history of more than two CNS metastases.
- Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or shows significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
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Determine if the administration of T-cells retrovirally transduced with the 2G-1 TCR, with preparative chemotherapy and IL-2, can cause the regression of metastatic RCC, and to identify the maximum tolerated dose for the 2G-1 TCr transduced cell...
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Sekundární výstupní opatření
Měření výsledku |
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Determine the toxicities of these T-cells administered in the above fashion, and to determine TCR and vector presence in the post treatment phase.
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- Motzer RJ, Michaelson MD, Rosenberg J, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Wilding G. Sunitinib efficacy against advanced renal cell carcinoma. J Urol. 2007 Nov;178(5):1883-7. doi: 10.1016/j.juro.2007.07.030. Epub 2007 Sep 17.
- Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007 Oct 10;25(29):4536-41. doi: 10.1200/JCO.2007.11.5154. Epub 2007 Sep 17.
- Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer. 2008 Jul 15;113(2):293-301. doi: 10.1002/cncr.23552.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
2. března 2009
Primární dokončení (Aktuální)
24. srpna 2012
Dokončení studie (Aktuální)
24. srpna 2012
Termíny zápisu do studia
První předloženo
17. června 2009
První předloženo, které splnilo kritéria kontroly kvality
17. června 2009
První zveřejněno (Odhad)
18. června 2009
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
9. dubna 2019
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
6. dubna 2019
Naposledy ověřeno
24. srpna 2012
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Novotvary podle histologického typu
- Novotvary
- Urologické novotvary
- Urogenitální novotvary
- Novotvary podle místa
- Onemocnění ledvin
- Urologická onemocnění
- Adenokarcinom
- Karcinom
- Novotvary, žlázové a epiteliální
- Novotvary ledvin
- Karcinom, renální buňka
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Antiinfekční látky
- Antivirová činidla
- Anti-HIV činidla
- Antiretrovirová činidla
- Antirevmatika
- Antineoplastická činidla
- Imunosupresivní látky
- Imunologické faktory
- Antineoplastická činidla, Alkylační
- Alkylační činidla
- Myeloablativní agonisté
- Aldesleukin
- Cyklofosfamid
- Fludarabin
Další identifikační čísla studie
- 090092
- 09-C-0092
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .