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Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

2022년 4월 15일 업데이트: Vincent T. Ho, MD, Dana-Farber Cancer Institute

A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant.

The device used to remove the α/βT cells in this study is:

-CliniMACS® TCR α/β Reagent System

연구 개요

상태

종료됨

정황

개입 / 치료

상세 설명

Patients who receive an allogeneic (using another person as the donor) stem cell transplant (SCT) are at risk for developing graft-versus-host disease (GVHD).

The word "graft" refers to the donor blood cells that you will receive during the transplant. The word "host" refers to the person receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of the participant's tissues.

GVHD may occur when the T cells (a type of white blood cell that helps protect the body from infection) from the donor react against normal tissues or organs in the body. There are two basic types of GVHD:

  • Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin, gastrointestinal tract (stomach and intestines) and liver.
  • Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many organs and significantly diminish quality of life.

To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a biopsy (a small sample of the participant's tissue to look at under the microscope) of the skin, gut, or, rarely, the liver.

In this research study, the investigator are investigating a pre-transplant intervention aimed to prevent GVHD by processing the donor product with the Miltenyi CliniMACS TCR α/β Reagent System. The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to the participant. By selectively removing this specific type of T cells from the donor product, the investigators hope to reduce the risk for GVHD without reducing the efficacy of the transplant.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved CliniMACS α/β T cell depletion system for use in the US, but this system is approved by the European Medicines Agency (EMA) and used in Europe

연구 유형

중재적

등록 (실제)

2

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, 02215
        • Dana Farber Cancer Institute

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 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Diagnoses and stage at time of transplant admission:

    • Acute leukemia (AML or ALL or MPAL) in first or subsequent remission
    • Myelodysplastic syndromes (MDS) with <10% marrow blasts
    • Myeloproliferative neoplasm (MPN) with <10% marrow blasts
    • CMML with less than 10% marrow blast
    • CML accelerated phase or second or subsequent chronic phase
    • Non-Hodgkin's lymphoma in PR or CR2 or beyond
    • Hodgkin lymphoma in PR or CR2 or beyond
  • Age 18-65 years
  • Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C, DRB1 and DQB1, based on allele level typing.
  • Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)
  • Patient deemed to be appropriate candidate for myeloablative conditioning transplantation.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patient with active HIV infection
  • Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)
  • Prior allogeneic hematopoietic stem cell transplantation
  • Impaired cardiac function- ejection fraction < 40%
  • Impaired pulmonary function- pretransplant FEV1, DLCO < 50%

  • Impaired renal function, based on

    --Serum creatinine > 2.0 mg/dl

  • Impaired liver function unrelated to primary disease, based on

    --ALT or AST > 3x ULN, or Total Bilirubin > 2.0mg/dl (with exception for known or suspected Gilbert's disease)

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry.
  • Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for HSCT, and if resumption of investigation agent is planned after HSCT, this must be approved by the study PI.
  • Participants with known active CNS disease. CNS disease that has been treated is eligible

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: TCR α/β Reagent System
  • The stem cell apheresis product will be depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device.
  • CD34+ stem cell counts will be obtained before and after processing with the Miltenyi ClinicMACs device
장치: ClinicMACs
The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Number of Participants With Severe Acute GVHD-free Survival
기간: 100 Days
Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT
100 Days

2차 결과 측정

결과 측정
측정값 설명
기간
Number of Participants With Grades II-IV Acute GVHD
기간: 2 years
Grades II-IV acute GVHD will be assessed at 2 years post-SCT. Grade I GVHD is characterized as mild disease, grade II as moderate, grade III as severe, and grade IV as life-threatening. Higher grades of acute GVHD are associated with worse outcomes. Acute GVHD will be staged by assessment of clinical manifestations in the skin, gastrointestinal tract, and liver.
2 years
Number of Participants With Chronic GVHD
기간: 2 years
Number of participants with chronic GVHD will be assessed at 2 years post-SCT.
2 years
Number of Participants With GVHD and Relapse Free Survival (GRFS)
기간: 2 years
GRFS will be defined as alive without having experienced grade III-IV acute GVHD, moderate/severe chronic GVHD, or relapse of underlying malignancy.
2 years
Number of Participants With Immunosuppression-free Survival
기간: 2 years
Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT.
2 years
Number of Participants With Hematologic Recovery
기간: 2 years
Hematologic recovery will be assessed in participants at 2 years post-SCT.
2 years
Number of Participants With Immune Reconstitution
기간: 2 years
Immune reconstitution will be assessed in participants at 2 years post-SCT.
2 years
Number of Participants With Disease Relapse
기간: 2 years
Disease relapse will be assessed in participants at 2 years post-SCT.
2 years
Number of Participants With Transplant-related Mortality
기간: 2 years
Participant transplant-related mortality will be assessed at 2 years post-SCT.
2 years
Number of Participants With Organ Toxicity
기간: 2 years
Participant organ toxicity will be assessed at 2 years post-SCT.
2 years
Rates of Infections
기간: 2 years
Participant rate of infections will be assessed at 2 years post-SCT.
2 years
Number of Participants With Relapse-free and Overall Survival
기간: 2 years
Number of participants with relapse-free and overall survival will be assessed at 2 years post-SCT.
2 years

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Dana-Farber Cancer Institute

수사관

  • 수석 연구원: Vincent T Ho, MD, 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 (실제)

2020년 1월 21일

기본 완료 (실제)

2021년 4월 26일

연구 완료 (실제)

2021년 4월 26일

연구 등록 날짜

최초 제출

2018년 10월 22일

QC 기준을 충족하는 최초 제출

2018년 10월 22일

처음 게시됨 (실제)

2018년 10월 24일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2022년 5월 10일

QC 기준을 충족하는 마지막 업데이트 제출

2022년 4월 15일

마지막으로 확인됨

2022년 4월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 18-270

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

예

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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