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Bone Marrow Transplant Using a Reduced Intensity Regimen That is Given in Two Steps

2016년 11월 28일 업데이트: Sidney Kimmel Cancer Center at Thomas Jefferson University

A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies Using Melphalan for T-Cell Tolerization

This is a research study involving the treatment of patients with hematological cancers with allogeneic (cells from a donor) hematopoietic stem cell transplant (HSCT). HSCT is often referred to as bone marrow transplant. Patients who are not expected to have long term survival after conventional therapy will undergo HSCT as a curative therapy after receiving front line therapy for their disease. This project is based on an HSCT approach that has been used at TJU since 2006 with the goal of optimizing this type of treatment further. In this new study, the investigators will substitute the chemotherapy agent, Melphalan (Mel), for cyclophosphamide (CY). Cyclophosphamide was used in the original trial. The research question is whether side effects are less using Mel and if donor T cells can be made tolerant to the recipient with the use of Mel. The proposed study is also more specific in terms of performance status and organ function entry criterion. The investigators observed in the original trial that patients with poor performance upon admission for transplant did not have as good outcomes.

Because many older patients are treated according to this type of transplant, the chemotherapy and radiation used are less intensive than other types of transplant. The name for this in the transplant field is a reduced intensity hematopoietic stem cell transplant. The abbreviations most used in this document are RIC for reduced intensity conditioning, HSCT which refers to the transplant itself, and MEL which refers to the drug, Melphalan.

연구 개요

상태

종료됨

정황

개입 / 치료

상세 설명

Twenty-nine patients in the Thomas Jefferson University (TJU) Blood and Marrow Transplantation Program have been treated on the research protocol, A Two Step Approach To Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies from HLA Partially-Matched Related Donors (TJU 2 Step RIC, TJU IRB# 06U.328) as of July, 2010. While treatment on this protocol has resulted in durable responses for many older patients and younger, heavily pretreated patients with hematological malignancies, poor performance status at the time of transplant and morbidities related to cyclophosphamide (CY) administration in the regimen have contributed to decreased survival. In addition, disease relapse after hematopoietic stem cell transplantation (HSCT) has been a major cause of mortality for those patients with disease at the time of transplant.

The objective of this research is to improve patient outcomes after treatment on the TJU 2 Step RIC protocol by refining the approach based on outcomes observed in the initial trial. More thorough assessment of performance status prior to HSCT and the substitution of the alkylating agent Melphalan (MEL) for CY to decrease CY-related toxicity while strengthening the anti-leukemic intensity of the regimen for patients with poor-risk disease will be the major strategies used to increase the efficacy of the regimen. MEL has shown efficacy against myeloid malignancies when used in conditioning in RIC HSCT. Patients with AML and MDS were the most common group treated on the initial TJU 2 Step RIC trial and also comprise the largest patient group treated in the TJU Medical Oncology Program.

연구 유형

중재적

등록 (실제)

8

단계

  • 2 단계
  • 1단계

연락처 및 위치

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연구 장소

  • 미국
    • Pennsylvania
      • Philadelphia, Pennsylvania, 미국, 19107
        • Thomas Jefferson University

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:

  1. Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. High risk is defined as:

    • Acute leukemia in 3rd or greater CR or with persistent disease
    • Myelodysplastic syndrome (MDS) other than RA or RARS subtypes.
    • Hodgkin's or Non-Hodgkin's lymphoma in 3rd or greater remission or with persistent disease.
    • Myeloma in 3rd or greater remission or with less than PR to most recent therapy.
    • Chronic myelogenous (or myeloid) leukemia (CML) resistant to STI therapy
  2. Patients must have a related donor who is at least a 4 antigen match at the HLA-A; B; C; DR loci.

  3. Patients must adequate organ function:

    • LVEF of > or = 50%
    • DLCO > or = 50% of predicted corrected for hemoglobin
    • Adequate liver function as defined by a serum bilirubin < or = 1.8, AST or ALT < or = 2.5X upper limit of normal
    • GFR of > or = 60 mL/min/1.73m2
  4. Performance status > or = 80% (TJU Karnofsky) for patients > or = 60 years old or > or = 70% for patients < 60.
  5. HCT-CI Score < or = 4 points for patients > or = 60 years old or < or = 5 points for patients < 60.
  6. Patients must be willing to use contraception if they have childbearing potential
  7. Able to give informed consent

Exclusion Criteria:

  1. Performance status < 80% (TJU Karnofsky) for patients > or = 60 years old or < 70% for patients < 60.
  2. HCT-CI Score > 4 points for patients > or = 60 years old or > 5 points for patients < 60.
  3. HIV positive
  4. Active involvement of the central nervous system with malignancy
  5. Inability to obtain informed consent
  6. Pregnancy
  7. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
  8. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of > or = 2 ugm/ml
  9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Donor Selection All donors are selected and screened for their ability to provide adequate infection-free apheresis products for the patient in a manner that does not put the donor at risk for negative consequences. Donor selection will be in compliance with 21 CFR 1271 and TJU BMT Program SOP CP: P009.03.

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: Transplant Treatment Group
All patients treated on this research study.
의약품: Fludarabine
Part of the conditioning regimen
다른 이름들:
  • 플루다라
  • 플루다라빈 인산염
의약품: Thiotepa
Part of the conditioning regimen
다른 이름들:
  • N,N'N'-트리에틸렌티오포스포르아미드
방사능: Total Body Irradiation (TBI)
There is one fraction of total body irradiation (2Gy) as part of the conditioning regimen.
다른 이름들:
  • 방사선 요법
생물학적: Donor Lymphocyte Infusion (DLI)
Immediately following the conditioning regimen of fludarabine, thiotepa, and TBI, the patient receives a set dose of their donor's T cells (DLI), After the DLI, the donor's T cells will react with the remaining parts of the recipients immune system.
다른 이름들:
  • 버피 코트 퓨전
의약품: Melphalan
Two days after the DLI, Melphalan will be given to eliminate the reacting T cells to avoid graft versus host disease. Non-activated T cells should not be affected by the Melphalan and remain to help fight infection.
다른 이름들:
  • 알케란
  • 멜팔란 염산염
  • MEL
장치: Hematopoietic stem cell transplantation (HSCT)

One day after the Melphalan ends, the patient will receive their donor's stem cells. This is the actual day of transplant.

The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.

다른 이름들:
  • 클리닉막스

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Phase 1: Defined Dose of Melphalan (MEL)
기간: 100 days post-transplant
To define the dose of MEL required for the establishment of peripheral T cell tolerance with concomitant immune reconstitution.
100 days post-transplant
Phase 2: Non-Relapse Mortality (NRM)
기간: 100 days post-treatment
To evaluate the 100 day non-relapse mortality (NRM) rate in patients undergoing HSCT treated on this successor TJU 2 Step RIC haploidentical regimen and compare it with that of the initial regimen.
100 days post-treatment

2차 결과 측정

결과 측정
측정값 설명
기간
Relapse Rate
기간: At 1 and 3 years
To compare relapse rates in patients undergoing HSCT treated on this successor TJU 2 Step RIC haploidentical regimen and compare it with that of the initial regimen.
At 1 and 3 years
GVHD Incidence and Severity
기간: At 1 and 3 years
To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treatment on this regimen using MEL for T cell tolerization as well as tacrolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis.
At 1 and 3 years
Engraftment Rate and Lymphoid Reconstitution
기간: 100 days post-transplant
To evaluate engraftment rates and lymphoid reconstitution in patients treated on this trial.
100 days post-transplant
Overall Survival
기간: At 1 and 3 years
To assess overall survival in patients undergoing HSCT treated on this trial.
At 1 and 3 years

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Sidney Kimmel Cancer Center at Thomas Jefferson University

간행물 및 유용한 링크

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

유용한 링크

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

2011년 4월 1일

기본 완료 (실제)

2012년 5월 1일

연구 완료 (실제)

2012년 8월 1일

연구 등록 날짜

최초 제출

2011년 5월 4일

QC 기준을 충족하는 최초 제출

2011년 5월 6일

처음 게시됨 (추정)

2011년 5월 9일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2016년 11월 29일

QC 기준을 충족하는 마지막 업데이트 제출

2016년 11월 28일

마지막으로 확인됨

2016년 10월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 10D.535
  • 2010-40 (기타 식별자: CCRRC)

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. .

Fludarabine에 대한 임상 시험

유사한 임상시험 검색

스폰서 및 공동 작업자

건강 상태

약물 개입

CROs by country

CROs in Armenia

정황

희귀 질병

약물 개입

식이 보충제

스폰서 / 협력자

위치

3
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