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T-Lymphocytes in Treating Patients With Epstein-Barr Virus-Positive Nasopharyngeal Cancer, NPC (NPC)

2012년 10월 5일 업데이트: Helen Heslop, Baylor College of Medicine

Administration of EBV-Specific T-Lymphocytes to Patients With EBV-Positive Nasopharyngeal Carcinoma

Patients have a type of cancer called nasopharyngeal cancer. This cancer has come back or not gone away or is at high risk for coming back after treatment (including the best treatment we know for nasopharyngeal cancer). We are asking patients to volunteer to be in a research study using special immune system cells called EBV-specific cytotoxic T lymphocytes, a new experimental therapy.

Most patients with nasopharyngeal cancer show evidence of infection with the virus that causes infectious mononucleosis, Epstein Barr virus (EBV), before or at the time of their diagnosis of nasopharyngeal cancer. EBV is found in the cancer cells of most patients with nasopharyngeal cancer, suggesting that it may play a role in causing this cancer. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells (called T cells) that have been trained to kill EBV-infected cells can survive in the patient's blood and affect the tumor.

We have treated other patients with different EBV positive cancers and have had variable results. Some patients have had some response to the treatment. Some patients have been cured by the treatment. It is not possible for us to predict if this treatment will work for nasopharyngeal cancer.

The purposes of this study are to find the largest safe dose of EBV specific cytotoxic T cells, to learn what the side effects are, and to see whether this therapy might help patients with nasopharyngeal cancer.

연구 개요

상태

완전한

정황

상세 설명

We will first test a biopsy of the tumor (that has already been done) to see if your tumor cells are EBV positive. If the patient is eligible, we will then take 60-70 ml (12-14 teaspoons) of blood from them. We will use this blood to grow more of the T cells in the laboratory. We will first grow an EBV-infected cell line by infecting the blood with EBV virus. This line will then be irradiated so it cannot grow and used to stimulate the T cells. This stimulation will train the T cells to kill cells with EBV on their surface. We will then grow these EBV-specific CTLs by more stimulation with EBV infected cells and a growth factor called Interleukin 2. Next, we will test the T cells to make sure that they kill the EBV-infected cells. If the number of T cells produced is low, we may need to obtain additional blood samples to make these cells.

The cells (which are the patient's own T cells) will be injected into them over 10 minutes, after pretreatment with Tylenol and Benadryl. A total of two doses will be given two weeks apart. All of the Treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or the Methodist Hospital.

We will follow the patient in the clinic after the injections. To learn more about the way the T cells are working and how long they last in the body, an extra 10-60 mls (2-12 teaspoons) of blood will be taken before the infusion and 3-4 days after the infusion (this is optional). Up to 40 ml (8 teaspoons) of blood will also be drawn at 1, 2, 4 and 6 weeks post-infusion, and then at 3, 6, 9, and 12 months. The blood may be drawn from the patient's central line at the time of the regular blood tests. We will use this blood to look at the immune response to the patient's cancer. Over the course of the study, up to 29 tablespoons of blood will be drawn.

Patients will also have repeat scans at 8 weeks after the first injections. If these show stable or improving disease they may (if the patient wishs) receive up to 6 extra doses of cells. These would be given every 1-3 months. If the patient has additional injections of cells after the first two infusions, we will take extra blood tests before each infusion, at the end of each infusion, 3-4 days after each infusion (day optional depending on patient preference), and at 1 and 2 weeks after each infusion. We will also do an extra scan between 1 and 3 months after the last infusion. Follow up will then continue every 3 months and will continue until 12 months after the last infusion.

연구 유형

중재적

등록 (실제)

25

단계

  • 1단계

연락처 및 위치

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연구 장소

    • Texas
      • Houston, Texas, 미국, 77030
        • The Methodist Hospital
      • Houston, Texas, 미국, 77030
        • Texas Children's Hospital

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 어린이
  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • All patients with NPC in first or subsequent relapse or with primary refractory disease or high risk (T3 or T4, or node positive disease) in whom the EBV genome or antigens have been demonstrated in tissue biopsies will be eligible for this trial. -Patients with a life expectancy >6 weeks
  • Patients with a Karnofsky score of >/= 50
  • No severe intercurrent infection.
  • Patient, parent/guardian able to give informed consent.
  • Patients with bilirubin <2x normal, SGOT <3x normal, and Hgb >8.0
  • Patients with a creatinine <2x normal for age
  • Patients should have been off other investigational therapy for one month prior to entry in this study.

Exclusion Criteria:

-Patients with a life expectancy of <6 weeks. -Patients with a Karnofsky score of < 50. -Patients with a severe intercurrent infection. -Patient, parent/guardian unable to give informed consent. -Patients with a bilirubin >2x normal. SGOT >3x normal or abnormal prothrombin time. -Patients with a creatinine >2x normal for age -Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.

Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigators discretion after approval by the CAGT Protocol Review Committee and the FDA reviewer.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: EBV specific CTL
autologous EBV specific CTLs

30-40cc of peripheral blood will be used to generate EBV specific CTLs

Group One:

Day 0 - 2 x 10^7 cells/m2 Day 14 - 2 x 10^7 cells/m2

Group Two:

Day 0 - 2 x 10^7 cells/m2 Day 14 - 1 x 10^8 cells/m2

Group Three:

Day 0 - 1 x 10^8 cells/m2 Day 14 - 2 x 10^8 cells/m2

다른 이름들:
  • EBV specific CTLs

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Safety of two IV injections of autologously derived Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs)
기간: 6 weeks
Patients will be enrolled at the first dose level and followed for six weeks after the second dose (which will constitute a course) for evaluation of any critical toxicity
6 weeks

2차 결과 측정

결과 측정
기간
the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines.
기간: 12 months
12 months

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

수사관

  • 수석 연구원: Helen E. Heslop, MD, Baylor College of Medicine

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2001년 8월 1일

기본 완료 (실제)

2007년 10월 1일

연구 완료 (실제)

2012년 6월 1일

연구 등록 날짜

최초 제출

2008년 2월 2일

QC 기준을 충족하는 최초 제출

2008년 2월 2일

처음 게시됨 (추정)

2008년 2월 6일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2012년 10월 10일

QC 기준을 충족하는 마지막 업데이트 제출

2012년 10월 5일

마지막으로 확인됨

2012년 10월 1일

추가 정보

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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