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중증 재생 불량성 빈혈 및 저형성 MDS에 대한 관련 없는 제대혈 이식 CordIn(TM), 제대혈 유래 체외 확장 줄기 및 전구 세포를 사용한 CordIn(TM)을 사용하여 생착 촉진 및 이식 결과 개선

2026년 9월 30일 업데이트: National Heart, Lung, and Blood Institute (NHLBI)

중증 재생 불량성 빈혈 및 저형성 MDS에 대한 비관련 제대혈 이식, CordIn, 제대혈 유래 체외 확장 줄기 및 전구 세포를 사용하여 생착 촉진 및 이식 결과 개선

Background:

Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are bone marrow diseases. People with these diseases usually need a bone marrow transplant. Researchers are testing ways to make stem cell transplant safer and more effective.

Objective:

To test if treating people with SAA or MDS with a co-infusion of blood stem cells from a family member and cord blood stem cells from an unrelated donor is safe and effective.

Eligibility:

Recipients ages 4-60 with SAA or MDS

Donors ages 4-75

Design:

Recipients will be screened with:

  • Blood, lung, and heart tests
  • Bone marrow biopsy
  • CT scan

Recipients will have an IV line placed into a vein in the neck. Starting 11 days before the transplant they will have several chemotherapy infusions and 1 30-minute radiation dose.

Recipients will get the donor cells through the IV line. They will stay in the hospital 3-4 weeks. After discharge, they will have visits:

  • First 3-4 months: 1-2 times weekly
  • Then every 6 months for 5 years

Donors will be screened with:

  • Physical exam
  • Medical history
  • Blood tests

Donors veins will be checked for suitability for stem cell collection. They may need an IV line to be placed in a thigh vein.

Donors will get Filgrastim or biosimilar (G-CSF) injections daily for 5-7 days. On the last day, they will have apheresis: Blood drawn from one arm or leg runs through a machine and into the other arm or leg. This may be repeated 2 days or 2-4 weeks later.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are life-threatening bone marrow disorders. For SAA patients, long term survival can be achieved with immunosuppressive treatment. However, of those patients treated with immunosuppressive therapy, one quarter to one third will not respond, and about 50 percent of responders will relapse.

Combined haplo-cord transplant as an alternative to cord or haploidentical donor alone transplantation has recently been shown to be a viable transplant option for SAA patients lacking an HLA matched donor. In our ongoing protocol 08-H-0046, we have utilized this approach in 25 patients with SAA with 23/25 patients having sustained engraftment and long-term disease free/transfusion free survival. However, engraftment patterns have varied substantially and in some patients, cord engraftment was profoundly delayed or never occurred. A number of strategies to expand hematopoietic progenitor cells (HPC) in vitro to improve engraftment and prevent graft rejection have recently been studied. Nicotimanide (NAM) expanded umbilical cord blood/unrelated cord blood (UCB) can be successfully engrafted in NOD/SCID mice (1) and humans (2) where they appear to have long-term repopulating potential. CordIn(TM) is a cryopreserved stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells. CordIn(TM) comprises: 1) Ex vivo expanded, umbilical cord blood-derived hematopoietic CD34+ progenitor cells ( (CordIn(TM) cultured fraction (CF)); and 2) the non-cultured cell fraction of the same CBU (CordIn(TM) Non-cultured Fraction (NF)) consisting of mature myeloid and lymphoid cells. Both fractions, i.e. CordIn(TM) CF and CordIn(TM) NF are kept frozen until they are infused on the day of transplantation.

This research protocol is therefore designed to evaluate the safety and effectiveness of transplantation with ex vivo expanded UCB (CordIn(TM)) to overcome the high incidence of graft rejection associated with conventional UCB for aplastic anemia, where graft rejection occurs in up to 50% of subjects. We believe, based on preliminary data, that transplantation of CordIn(TM) will not only lead to rapid engraftment, but will also lead to sustained hematopoiesis, expedited immune recovery, and will reduce the chance of cord graft failure in this setting, potentially obviating the need for co-transplanting haploidentical CD34+ cells as a stem cell back-up. This phase II study is designed to have two cohorts: cohort 1 is intended to establish (in as safe a manner as possible) preliminary pilot data to support the capacity for the CordIn unit to engraft in patients with SAA in the presence of haplo CD34+ cells. For cohort 1, three to six subjects will be conditioned then will be transplanted with the thawed CordIn(TM) unit (consisting of the cultured fraction and the non-cultured fraction of the same CBU) and approximately 3 x 10^6 CD34+ cells/kg from a haploidentical donor which will serve as a backup stem cell source should cord graft failure occur. If 3 of the first 3 to 4 subjects or 4 of 6 subjects achieve early and sustained engraftment (defined as ANC >500 cells/ul by day 26 and a calculated cord ANC >500 cells /ul by day 42 sustained at day 100), the study will move to cohort 2 where up to 23 subsequent subjects will be transplanted with the CordIn(TM) unit alone.

The primary objective of the Phase II study is to evaluate the ability of the CordIn(TM) unit to achieve sustained early engraftment. Secondary endpoints will include 100 day and 200 day treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease. Health related quality of life will also be assessed as secondary outcome measure.

연구 유형

중재적

등록 (추정된)

37

단계

  • 2 단계
  • 1단계

연락처 및 위치

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

연구 연락처

연구 연락처 백업

연구 장소

  • 미국
    • Maryland
      • Bethesda, Maryland, 미국, 20892
        • 모병
        • National Institutes of Health Clinical Center
        • 연락하다:
          • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
          • 전화번호: TTY8664111010 800-411-1222
          • 이메일: prpl@cc.nih.gov

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

4년 (어린이, 성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

  • INCLUSION CRITERIA - RECIPIENT:
  • Diagnosed with severe aplastic anemia with bone marrow cellularity <30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count <=1000 cells/ uL or for patients receiving granulocyte transfusions, absolute neutrophil count <=1000 cells/ uL before beginning granulocyte transfusions).

OR

History of severe aplastic anemia transformed to MDS that meet the following criteria: a) International Prognostic Scoring System (IPSS) risk category of INT-1 or greater, b) < 5% myeloblasts and < 30% of cellularity in the bone marrow on screening morphologic analysis.

-Intolerance of or failure to respond to immunosuppressive therapy. This also includes patients who have failed immunosuppressive therapy with ATG and cyclosporine or therapy with cyclosporine combined with eltrombopag in those who are intolerant of or do not have access to treatment with ATG.

Identification of either a) at least one alternative donor (i.e. HLA- haploidentical related donor (i.e. >=5/10 HLA match: HLA-A, B, C, DR, and DQ loci) or >=9/10 HLA matched unrelated donor) who is available to serve as a stem cell donor for a salvage allogeneic transplant in the event that the CordIn(TM) unit has been rejected or b) umbilical cord blood unit/s that can be used for a salvage cord blood transplant in the event that the CordIn(TM) unit has been rejected.

-Availability of at least one >=4/8 HLA matched (HLA-A, B, C, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP).

The cord blood unit must contain a minimum TNC of at least 1.8 x 10^9 and at least 1.5x10^7/kg TNC and at least 8 x 10^6 CD34+ cells (all doses prior to thawing).

Exception: Cord units containing at least 8 x 10^6 CD34+ cells but less than 1.8 x 10^9 TNC may be eligible for use on this trial if

  1. the pre-expansion CD34/kg recipient cell number is at least 1.5 x 10^5 /kg

    AND

  2. approval for use of this cord unit for expansion is granted by Gamida Cell.

  3. the final cell counts on the cultured and non-cultured fractions meet the IND specified minimal release criteria.

    • The CBU will have undergone volume reduction (both plasma and red blood cell depletion) prior to cryopreservation. All CBUs should be procured from public banks that meet local applicable regulations.
    • Ages 4-60 years inclusive.
    • Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian.

EXCLUSION CRITERIA - RECIPIENT (ANY OF THE FOLLOWING):

  • Availability of an HLA identical (12/12) matched related or unrelated donor who is available within optimal timeline and suitable considering graft source and established donor selection factors (e.g. age, sex, viral exposure, ABO compatibility, pregnancy status, etc) per PI discretion.
  • ECOG performance status of 2 or more.
  • Major anticipated illness or organ failure incompatible with survival from transplant.
  • Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy, if of childbearing potential for one year.
  • Diagnosis of Fanconi s anemia (by chromosome breakage study).
  • Diffusion capacity of carbon monoxide (DLCO) <40% using DLCO corrected for Hgb or lung volumes (patients under the age of 10 may be excluded from this criterion if they have difficulty performing the test correctly and thus are unable to have their DLCO assessed).
  • Left ventricular ejection fraction < 40% (evaluated by ECHO).
  • Transaminases > 5x upper limit of normal.
  • Serum bilirubin >4 mg/dl.
  • Creatinine clearance < 50 cc/min/BSAm^2 by 24-hour urine collection adjusted by body surface area.
  • Serum creatinine > 2.5 mg/dl
  • Presence of an active infection not adequately responding to appropriate therapy.
  • History of a malignant disease liable to relapse or progress within 5 years.
  • Allergy to bovine, Gentamicin, or to any product which may interfere with the treatment.
  • Presence of donor-specific antibodies (DSA) to the umbilical cord blood unit and for cohort 1, to the haplo-identical donor.

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: 순차적 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 1

CordIn is a cryopreserved stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells.
생물학적: Omidubicel (former CordIn)

Stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic umbilical/unrelated cord blood (UCB) cells. CordIn(TM) comprises: 1) cord blood-derived ex vivo expanded CD133+ cells (CordIn (TM) cultured fraction (CF)); and 2) the non-cultured cell fraction (CD133-) of the same CBU (CordIn(TM) Non-cultured Fraction (NF)). Both fractions, i.e. CordIn(TM) CF and CordIn(TM) NF are kept frozen until they are infused on the day of transplantation.

장치: Miltenyi CliniMACS(R) CD34 Reagent System

The CliniMACS CD34 Reagent System is a medical device system that is designed for the in vitro enrichment of CD34+ target cells from heterogeneous hematologic cell populations. The process of CD34+ cell selection results in simultaneous passive depletion of donor lymphocytes, potentially obviating the need for immunosuppressive drugs to prevent GVHD.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Cord engraftment
기간: At or before day 100

Cord engraftment
At or before day 100

2차 결과 측정

결과 측정
측정값 설명
기간
Treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease
기간: 100 day and 200 day

treatment related mortality
100 day and 200 day

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Heart, Lung, and Blood Institute (NHLBI)

수사관

  • 수석 연구원: Richard W Childs, M.D., National Heart, Lung, and Blood Institute (NHLBI)

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 (실제)

2017년 6월 13일

기본 완료 (추정된)

2027년 4월 28일

연구 완료 (추정된)

2032년 3월 1일

연구 등록 날짜

최초 제출

2017년 5월 31일

QC 기준을 충족하는 최초 제출

2017년 6월 1일

처음 게시됨 (실제)

2017년 6월 2일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 10월 1일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 30일

마지막으로 확인됨

2026년 9월 28일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 170091
  • 17-H-0091

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

미정

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

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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