Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers (ProT4)
Multicenter Randomized Phase II Study to Evaluate the Efficacy of Prophylactic Transfer of CD4 Lymphocytes After T-cell Depleted Reduced Intensity HLA-Identical Sibling Transplantation for Haematological Cancers
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving alemtuzumab before transplant and cyclosporine after transplant, may stop this from happening.
PURPOSE: This randomized phase II trial is studying donor lymphocyte infusion after stem cell transplant in preventing cancer relapse or cancer progression in patients with follicular lymphoma, small lymphocytic non-Hodgkin lymphoma, or chronic lymphocytic leukemia.
연구 개요
상세 설명
OBJECTIVES:
Primary
- To evaluate the effect of prophylactic transfer of donor CD4 cells after T-cell depleted reduced-intensity HLA-identical sibling transplantation upon the risk of relapse or progression in patients with haematological cancers (e.g. NHL, HL, CLL/PLL, PCM, AML, ALL, MDS or CMML depending on the disease status).
Secondary
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the risk of graft-versus-host disease (GvHD) in these patients.
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the rates of conversion to full donor chimerism in peripheral blood in these patients.
- To determine the effect of prophylactic transfer of donor CD4 cells upon immune reconstitution in these patients.
- To evaluate the impact of prophylactic transfer of donor CD4 cells upon non-relapse mortality and overall survival of these patients.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV, melphalan IV, and alemtuzumab IV as reduced intensity conditioning for T-cell depletion followed by a reduced-intensity HLA-identical sibling stem cell transplantation on day 0. Withdrawal of cyclosporine immunosuppression therapy commence at day 40 with tapering over a period of 3-4 weeks, according to the discretion of the PI. Patients are reassessed between day 70-90 post-transplantation. Patients with stable engraftment, no significant graft-versus-host disease, and no early relapse or progression are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive an allogeneic CD4 donor lymphocyte infusion (DLI) at a dose of 1 x10^6 CD4 cells/kg body weight without any other medication once between day 100-120.
- Arm II: Patients receive no further treatment.
Patients undergo blood sample collection for chimerism studies and translational research.
After completion of study treatment, patients are followed up periodically for 1 years and then annually.
Peer Reviewed and Funded or Endorsed by Bloodwise.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Birmingham, 영국
- Birmingham Heartlands Hospital
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Bristol, 영국
- Bristol Royal Hospital for Children
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Cambridge, 영국
- Addenbrooke's Hospital
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Glasgow, 영국
- Beatson West of Scotland Cancer Centre
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Leeds, 영국
- St James's University Hospital
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Leicester, 영국
- Leicester Royal Infirmary
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London, 영국
- University College Hospital London (UCLH)
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Manchester, 영국
- Christie Hospital
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Nottingham, 영국
- Nottingham City Hospital
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Sheffield, 영국
- Royal Hallamshire Hospital
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Southampton, 영국
- University Hospitals Southampton
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
At registration (pre-transplant)
Haematological cancer which can be ONE OF the following:
- Non-Hodgkin's lymphoma (NHL) in CR or PR
- Hodgkin's lymphoma (HL) in CR or PR
- Chronic (Pro-)lymphocytic leukaemia (CLL/PLL) in CR or PR
- Plasma cell myeloma (PCM) in CR, VGPR or PR
- Acute myeloid leukaemia (AML) in CR
- Acute lymphoblastic leukaemia (ALL) in CR
- Myelodysplastic syndrome (MDS) < 10% blasts in bone marrow
- Chronic myelomonocytic leukaemia (CMML) < 10% blasts in bone marrow
- Have undergone disease reassessment within 8 weeks prior to registration
HLA-identical sibling transplant to be performed using one of the following reduced intensity alemtuzumab-containing conditioning regimens:
- Fludarabine-busulphan-alemtuzumab
- Fludarabine-melphalan-alemtuzumab
- BCNU-etoposide-cytarabine-melphalan (BEAM)-alemtuzumab
- CCNU-etoposide-cytarabine-melphalan (LEAM)-alemtuzumab
- Aged ≥18 years, and <70 years
- Written informed consent
Exclusion Criteria
- Women who are pregnant or breast-feeding
- Life expectancy of <8 weeks
- Currently taking part in any other interventional clinical research study (involving any IMP, ATMP or cellular therapy)
- Organ dysfunction: Creatinine >200μmol/l, Bilirubin >50μmol/l, or AST/ALT > 3x ULN
Post-transplant
- Active acute GvHD
- Prior grade II-IV GvHD
- Relapse or progressive disease
- Primary or secondary graft failure
- Other cellular therapies
- Requirement for ongoing immunosuppression
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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다른: CD4 DLI
Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
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Patients will receive CD4 DLI between day 70 to 115 post transplant
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다른: No DLI
Patients will receive no DLI post transplant as trial treatment.
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Patients will not receive DLI as trial treatment
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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Progression-free survival at 1 year post-transplant
기간: during the study and end of study
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during the study and end of study
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
기간: End of study
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End of study
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Incidence of infection requiring inpatient treatment
기간: during the study and end of study
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during the study and end of study
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Rate of reconstitution of T-cell subsets and viral-specific immunity
기간: End of study
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End of study
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Cumulative incidence of non-relapse mortality at 1 year
기간: End of study
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End of study
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Overall survival and non-relapse mortality
기간: End of study
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End of study
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Incidence, grade, or pattern of graft-versus-host disease
기간: during the study and end of study
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during the study and end of study
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공동 작업자 및 조사자
수사관
- 수석 연구원: Ronjon Chakraverty, Professor, University College Hospital London; UCL Cancer Institute
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (예상)
연구 완료 (예상)
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
- 비호지킨 림프종
- 호지킨 림프종
- 발덴스트롬 마크로글로불린혈증
- 3기 1등급 여포성 림프종
- 3기 2등급 여포성 림프종
- IV기 1등급 여포성 림프종
- IV기 2등급 여포성 림프종
- 골수 형성 이상 증후군
- 재발성 등급 1 여포성 림프종
- 재발성 등급 2 여포성 림프종
- 재발성 소림프구성 림프종
- 3기 소림프구성 림프종
- 4기 소림프구성 림프종
- 난치성 만성 림프 구성 백혈병
- 3기 만성 림프구성 백혈병
- IV기 만성 림프구성 백혈병
- 이식편대숙주병
- 급성 골수성 백혈병
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
추가 관련 MeSH 약관
기타 연구 ID 번호
- UCL/10/0241
- UCL-10/0241 (기타 식별자: Sponsor)
- LRF-09041 (기타 보조금/기금 번호: Leukaemia & Lymphoma Research)
- EU-21081 (기타 식별자)
- CRUK-UCL-PROT4 (기타 식별자: Cancer Research UK & UCL Cancer Trials Centre)
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