- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00376480
Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant
Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia
RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.
연구 개요
상태
상세 설명
OBJECTIVES:
Primary
- Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
- Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
- Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization.
- Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC.
- Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.
Secondary
- Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
- Assess, in vitro, the function of immune cells engrafted in these patients.
- Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
- Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
- Describe the patterns of opportunistic infections in these patients.
OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except dose level 1 are stratified according to age (under 17 [pediatric] vs 17 and over [adult]).
- Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34-selected PBSCT on day 0.
- Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease, patients undergo allogeneic or autologous PBMC infusion on day 35 or 42.
Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity.
After completion of study, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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California
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Los Angeles, California, 미국, 90027-0700
- Childrens Hospital Los Angeles
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Florida
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Gainesville, Florida, 미국, 32610
- University of Florida Health Science Center - Gainesville
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Massachusetts
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, 미국, 02115
- Children's Hospital Boston
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Boston, Massachusetts, 미국, 02115
- Dana Farber Cancer Institute
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Texas
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Houston, Texas, 미국, 77030-4009
- M. D. Anderson Cancer Center at University of Texas
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Acute lymphocytic leukemia
In ≥ second complete remission (CR), defined as < 5% blasts in bone marrow (BM) and no active extramedullary disease OR in first CR with any of the following high risk features:
- History of induction failure
- Philadelphia chromosome positive
- t(4;11) by cytogenetic analysis
- Any infant with MLL rearrangements on cytogenetic analysis
- No relapse with isolated extramedullary disease after completion of prior treatment
Acute myeloid leukemia
- Failed induction therapy after < 3 courses
In ≥ second CR, defined as < 5% blasts in BM and no active extramedullary disease OR in first CR with any of the following high-risk features:
- History of induction failure = 5q- or monosomy 7 cytogenetic findings
Any of the following myelodysplastic syndromes:
- Refractory anemia (RA) with excess blasts (RAEB) with a high International Prognostic Scoring System (IPSS) score or score of intermediate-1(INT-1) or intermediate-2 (INT-2)
- RAEB in transformation with INT-1, INT-2, or high IPSS score
- RA with INT-2 score
Patients must have a healthy, related donor who is at least genotypically HLA-A, B, C, and DR haploidentical to the patient
- No suitably matched family donor defined by genotypic or phenotypic identity for ≥ 5/6 A, B, or DR loci
- No immediately available genotypically matched (6/6) unrelated marrow donor
- No immediately available umbilical cord blood donor with suitable cell dose after a search ≥ 2 months
- Patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search are eligible
- Has a parent with a haplotype that is disparate from that of the donor for the haplotype shared by the patient and parent, but not shared by the patient and donor OR patient is able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis
- No active CNS disease
PATIENT CHARACTERISTICS:
- Room air O_2 saturation > 95% unless the lungs are involved with disease
- No clinical evidence of pulmonary insufficiency unless the lungs are involved with disease
- AST and ALT < 3 times upper limit of normal (ULN)*
- Bilirubin < 2.0 mg/dL*
- Creatinine < 2 times ULN OR creatinine clearance or glomerular filtration rate > 50% of the lower limit of normal
- LVEF > 45% OR shortening fraction > 20%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection, defined as absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms
- No evidence of HIV infection OR known HIV positivity NOTE: *Does not apply if liver is involved with disease
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior stem cell transplantation
- No other concurrent immunosuppressive therapy
공부 계획
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: administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Feasibility of making and administering the adoptive T cell product
기간: from conditioning through administration of anergized cells on day 35-42
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ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.
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from conditioning through administration of anergized cells on day 35-42
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Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant
기간: the period from aDLI infusion through D100
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rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction
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the period from aDLI infusion through D100
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Alloreactivity engendered by administering the adoptive T cell product
기간: from cell infusion through day 100
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occurrence and severity of acute GVHD
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from cell infusion through day 100
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Efficacy in restoring adaptive immunity
기간: from aDLI thorough 1 year
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incidence of viral infection and type of immune reconstitution by phenotype and function of T cells
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from aDLI thorough 1 year
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공동 작업자 및 조사자
수사관
- 연구 의자: Eva Guinan, MD, Dana-Farber Cancer Institute
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
- 난치성 빈혈
- 과도한 돌풍을 동반한 난치성 빈혈
- 변형에 과도한 모세포가 있는 난치성 빈혈
- 새로운 골수이형성 증후군
- 이전에 치료받은 골수이형성 증후군
- 속발성 골수이형성 증후군
- 11q23(MLL) 이상이 있는 성인 급성 골수성 백혈병
- inv(16)(p13;q22)가 있는 성인 급성 골수성 백혈병
- t(15;17)(q22;q12)가 있는 성인 급성 골수성 백혈병
- t(16;16)(p13;q22)가 있는 성인 급성 골수성 백혈병
- t(8;21)(q22;q22)가 있는 성인 급성 골수성 백혈병
- 속발성 급성 골수성 백혈병
- 차도가 있는 소아 급성 림프구성 백혈병
- 완화된 소아 급성 골수성 백혈병
- 소아 골수이형성 증후군
- 차도가 있는 성인 급성 골수성 백혈병
- 차도가 있는 성인 급성 림프구성 백혈병
추가 관련 MeSH 약관
기타 연구 ID 번호
- 05-030
- P30CA006516 (미국 NIH 보조금/계약)
- P01CA100265 (미국 NIH 보조금/계약)
- MDA-2005-0695
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
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. .
메틸프레드니솔론에 대한 임상 시험
-
Sun Yat-sen University알려지지 않은
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Nanjing University School of Medicine모병
-
Dana-Farber Cancer InstituteGlaxoSmithKline; National Comprehensive Cancer Network종료됨
-
Germans Trias i Pujol Hospital완전한
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Fondazione IRCCS Ca' Granda, Ospedale Maggiore...Azienda Ospedaliero, Universitaria Pisana; Istituto Auxologico Italiano; Azienda Ospedaliera... 그리고 다른 협력자들모병