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Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD

2020년 4월 7일 업데이트: Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute

Phase II Trial of Natalizumab (Tysabri®) Plus Prednisone for Initial Therapy of Acute Graft Versus Host Disease (aGVHD) of the Gastrointestinal Tract

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug Natalizumab in treating Acute Graft-Versus-Host Disease (GVHD) in the Gastrointestinal (GI) Tract.

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

Natalizumab is a drug that was initially discovered as a treatment for autoimmune conditions. Natalizumab has been approved for use in patients with Multiple Sclerosis and Crohn's disease. In these diseases, the drug works to inhibit dysfunctional immune cells that are responsible for the symptoms seen in these diseases. Acute graft versus host disease is caused by a similar dysfunction of immune cells; Natalizumab is thought to inhibit these immune cells, similarly to how it does in Multiple Sclerosis and Crohn's disease. In this research study,the investigators are looking to see whether Natalizumab provides additional benefit to patients receiving standard treatment for acute graft versus host disease of the gastrointestinal tract.

Participants who fulfill eligibility criteria will be entered into the trial to receive Natalizumab.

  • Participant will receive a dose of the natalizumab through intravenous infusion. Participants may receive a second dose at Day 28 if they experience a partial response or very good partial response.
  • Scheduled Physical Examination at screening, during the week of first dose and at 28 days, 56 days, 100 days, 180 days and one year.

연구 유형

중재적

등록 (실제)

21

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 미국
    • Massachusetts
      • Boston, Massachusetts, 미국, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, 미국, 02114
        • Massachusetts General 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

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Participants must meet the following criteria on screening examination to be eligible to participate in the study:
  • Participants must have acute Graft-Versus-Host Disease (GVHD) of the lower gastrointestinal tract as defined by the clinical impression of the treating physician, requiring systemic treatment. Minimum criteria for GI GVHD includes diarrhea of greater than 500 mL/day. Biopsy of the GI tract is required for study entry and must confirm the diagnosis of acute GVHD. Stool samples to rule out infectious causes of diarrhea, including norovirus, Clostridium difficile and other clinically indicated infections must also be negative. Eligibility includes:
  • Acute GVHD developing after allogeneic hematopoietic stem cell transplantation (HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood. Recipients of non-myeloablative, reduced intensity and myeloablative transplants are eligible.
  • Patients who develop acute GVHD after donor lymphocyte infusion (DLI) are eligible.
  • There is no specified time window after day 0 of transplant as acute GVHD is only defined by clinical manifestations.
  • Patients must have experienced neutrophil engraftment after HSCT as defined by absolute neutrophil counts ≥ 500 / µL × 3 consecutive measurements. Absolute neutrophil count (ANC) should be calculated using the standard formula (Neut + Bands)(WBC × 101).
  • The presence of hepatic, upper GI and/or cutaneous acute GVHD is permitted.
  • Steroids can be started up to 7 days prior to the administration of natalizumab.
  • Age ≥ 18
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
  • Patients with the entity of Acute/Chronic GVHD overlap syndromes.
  • Requiring mechanical ventilation
  • Vasopressor requirement
  • Concurrent hepatic veno-occlusive disease (VOD) based on clinical examination
  • Karnofsky performance status < 30
  • Participants may not be receiving any other study agents for at least 7 days prior to enrollment
  • Prior use of natalizumab for any reason is not allowed
  • Pregnant women are excluded from this study because of the potential teratogenic effects of natalizumab. Because natalizumab enters breast milk, and the effect is unknown in infants, breastfeeding should be discontinued if the mother is treated with natalizumab.

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: Natalizumab

Natalizumab-

  • (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
  • At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
  • If participants have no response after one dose, they will be not be given a second dose.
  • Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
  • Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
  • Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert
의약품: 메틸프레드니솔론
다른 이름들:
  • 스테로이드
의약품: 나탈리주맙
다른 이름들:
  • 타이사브리®

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
GVHD-free Survival Rate
기간: Day 56
Graft-versus-host disease (GVHD) free survival is defined as achieving complete response without death or relapse or requiring secondary immunosuppressive therapy . Proportions are reported descriptively. GVHD-free survival was assessed using the Kaplan-Meier method.
Day 56

2차 결과 측정

결과 측정
측정값 설명
기간
Graft-verus-host Disease (GVHD) Response Rate
기간: 28 Days, 56 Days
  • Complete Response (CR) is defined as resolution of all signs and symptoms of acute GVHD.
  • Very Good Partial Response (VGPR) is defined by no rash or residual erythematous rash involving less than 25% of the body surface, and total serum bilirubin concentration less than 2 mg/dL or less than 25% of baseline at enrollment and tolerating food or enteral feeding, predominantly formed stools, no overt gastrointestinal bleeding or abdominal cramping, and no more than occasional nausea and vomiting.
  • Partial Response (PR) is defined as an improvement of one stage in one or more organs without progression in any other organ.
  • Non-response (NR) is defined as no reduction in any GVHD organ staging.
  • Progression is defined as either new organ involvement on day +8 or thereafter, or increased organ specific symptoms sufficient to increase the organ stage by one or more or the initiation of an additional GVHD agent.
  • Overall Response Rate (ORR) is the sum of CR, VGPR, and PR.
28 Days, 56 Days
GI aGVHD Response Rate
기간: Day 28, Day 56
Gastrointestinal (GI) acute graft-versus-host disease (GVHD) Response is defined by complete response, very good partial response, or partial response in signs and symptoms of GI aGVHD.
Day 28, Day 56
Overall Survival (OS) Rate
기간: 2 years
Overall survival (OS) is defined from the date of natalizumab infusion to death or censored at last clinical evaluation. OS was estimated using the Kaplan-Meier method.
2 years
Rate of GVHD Flares
기간: by Day 28
Number of subjects who experienced graft-versus-host disease (GVHD) flares requiring therapy after initial complete response (CR) or partial response (PR) by day 28 after the first dose of Natalizumab.
by Day 28
Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.
기간: Day 28, 56, and 100
Median percentage steroid dose was reduced at Day 28, Day 56, and Day 100 in comparison to steroid dose at first administration of Natalizumab.
Day 28, 56, and 100

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Dana-Farber Cancer Institute

협력자

Biogen

수사관

  • 수석 연구원: Corey Cutler, MD, MPH, Dana-Farber Cancer Institute

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

2015년 1월 1일

기본 완료 (실제)

2019년 2월 1일

연구 완료 (실제)

2019년 2월 1일

연구 등록 날짜

최초 제출

2014년 6월 25일

QC 기준을 충족하는 최초 제출

2014년 6월 25일

처음 게시됨 (추정)

2014년 6월 26일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2020년 4월 17일

QC 기준을 충족하는 마지막 업데이트 제출

2020년 4월 7일

마지막으로 확인됨

2020년 4월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 14-140

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