Fludarabine and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Lymphocytic Leukemia or Waldenstrom's Macroglobulinemia
Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia
RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal 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 methotrexate, cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
PURPOSE: This phase I/II trial is studying the side effects of giving fludarabine together with cyclophosphamide and to see how well they work in treating patients who are undergoing donor stem cell transplant for B-cell chronic lymphocytic leukemia or Waldenström's macroglobulinemia.
연구 개요
상태
정황
상세 설명
OBJECTIVES:
Primary
- Determine the feasibility and safety of induction therapy comprising fludarabine and cyclophosphamide followed by allogeneic stem cell transplantation in patients with high-risk B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia).
Secondary
- Determine the incidence and kinetics of clinical and molecular remissions in patients treated with this regimen.
- Determine event-free and overall survival of patients treated with this regimen.
- Determine the duration of clinical and molecular remission in relation to the underlying cytogenetic deviation in patients treated with this regimen.
- Determine the kinetics and extent of lympho-hematopoietic donor chimerism in patients treated with this regimen.
OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.
- Cytoreductive therapy: Patients receive up to 3 courses of cytoreductive therapy comprising fludarabine IV and cyclophosphamide IV on days 1-3 (with or without rituximab IV on day 1). Patients refractory to fludarabine-containing therapy may receive alemtuzumab IV for 12 weeks OR any other cytotoxic salvage regimen for cytoreduction.
- Conditioning regimen: Patients receive 1 of the following conditioning regimens*:
NOTE: *Patients who did not achieve partial response after cytoreductive therapy receive regimen 3.
- Regimen 1: Patients receive fludarabine IV and cyclophosphamide IV on days -7 to -3. If stem cells are collected from an unrelated donor, patients also receive anti-thymocyte globulin (ATG) IV on days -4 to -1.
- Regimen 2: Patients undergo total-body irradiation on day -9. Patients then receive alemtuzumab IV on days -8 to -4 and fludarabine IV and cyclophosphamide IV on days -6 to -2.
Regimen 3: Patients receive fludarabine IV on days -7 to -3, busulfan IV or orally on days -7 to -5, and cyclophosphamide IV on days -3 to -2. If stem cells are collected from an unrelated donor, patients also receive ATG on days -3 to -1.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily starting on day 5 and continuing until blood count recover.
- Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV beginning on day -1 and continuing until approximately day 100. Patients treated with conditioning regimen 1 or 3 also receive methotrexate IV on days 1, 3, and 6 OR oral mycophenolate mofetil twice daily on days 0-50. Patients with evidence of residual disease at least 4 weeks after completion of cyclosporine undergo donor lymphocyte infusion (DLI).
- DLI: The donor T-lymphocytes are collected from the PBSCT donor without prior G-CSF mobilization. Patients receive DLI every 8 weeks in the presence of residual disease and the absence of GVHD.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
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Berlin, 독일, 12200
- Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
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Essen, 독일, 45122
- Universitaetsklinikum Essen
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Goettingen, 독일, 37075
- Universitaetsklinikum Goettingen
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Hamburg, 독일, D-20099
- Asklepios Klinik St. Georg
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Hannover, 독일, 30625
- Medizinische Hochschule Hannover
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Heidelberg, 독일, D-69120
- Universitaets-Kinderklinik Heidelberg
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Homburg, 독일, 66421
- Universitaetsklinikum des Saarlandes
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Idar-Oberstein, 독일, D-55743
- Clinic for Bone Marrow Transplantation and Hematology and Oncology
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Kiel, 독일, 24116
- University Hospital Schleswig-Holstein - Kiel Campus
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Leipzig, 독일, 04103
- University Hospital of Leipzig
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Regensburg, 독일, 93053
- Klinikum der Universitaet Regensburg
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Ulm, 독일, 89081
- Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
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Quebec
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Montreal, Quebec, 캐나다, H1T 2M4
- Maisonneuve-Rosemont Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
DISEASE CHARACTERISTICS:
Diagnosis of B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia)
Must have poor prognostic features and low probability of successful autografting, defined by one of the following criteria:
Progressive disease with unfavorable cytogenetics (deletion or mutation of critical regions on chromosomes 11q and/or 17p [p53]; and/or unmutated status of the immunoglobulin V_H gene region; and/or usage of the V_H 3-21 gene), defined as 1 of the following:
- Doubling of lymphocyte count or nodal involvement within 3 months or less
- Progressive decline of platelet count and/or hemoglobin values defining Binet stage C disease (or to 50% or less of baseline values within 3 months) not due to immune mechanisms
- Symptomatic splenomegaly
- Discomfort or imminent complications due to large tumor masses
- B symptoms
- Refractory disease or early relapse (within 12 months) after treatment with a fludarabine-containing regimen
- Relapsed after autologous stem cell transplant (SCT)
- Insufficient stem cell harvest for intended autologous SCT
- Presence of a clonal CDR III rearrangement detected by polymerase chain reaction
- No Richter's syndrome
- HLA-identical sibling or unrelated donor available
PATIENT CHARACTERISTICS:
- ECOG performance status ≤ 1
- Creatinine clearance > 60 mL/min
- SGOT, SGPT, and bilirubin < 2 times normal
- Normal cardiac function determined by ECG and echocardiographic examination
- Inspiratory vital capacity, FEV_1, and DLCO > 50% of predicted
- No serious localized or systemic infections
- No other concurrent malignant disease
- No impaired organ function
- No uncontrolled diabetes
- No uncontrolled hypertension
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No HIV infection
- No hepatitis B or C infection
- No concurrent alcohol or drug abuse
- No dementia or altered mental status that would preclude giving informed consent
PRIOR CONCURRENT THERAPY:
- Not specified
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 |
|---|---|
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실험적: Allogeneic stem cell transplantation
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
|---|
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Feasibility as measured by the proportion of eligible patients completing the transplant procedure successfully
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Safety as measured by a treatment-related mortality of < 25% at 2 years following transplant
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2차 결과 측정
결과 측정 |
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Clinical remission rate by NIH criteria at 12 months following transplant
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Minimal residual disease negativity rate as measured by high-resolution flow or CDR PCR at 12 months following transplant
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Chimerism as measured by STR-PCR at 12 months following transplant
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Event-free and overall survival at 5 years following transplant
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공동 작업자 및 조사자
수사관
- 연구 의자: Peter Dreger, Universitaets-Kinderklinik Heidelberg
간행물 및 유용한 링크
일반 간행물
- Dreger P, Dohner H, Ritgen M, Bottcher S, Busch R, Dietrich S, Bunjes D, Cohen S, Schubert J, Hegenbart U, Beelen D, Zeis M, Stadler M, Hasenkamp J, Uharek L, Scheid C, Humpe A, Zenz T, Winkler D, Hallek M, Kneba M, Schmitz N, Stilgenbauer S; German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010 Oct 7;116(14):2438-47. doi: 10.1182/blood-2010-03-275420. Epub 2010 Jul 1.
- Ritgen M, Bottcher S, Stilgenbauer S, Bunjes D, Schubert J, Cohen S, Humpe A, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P; German CLL Study Group. Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial. Leukemia. 2008 Jul;22(7):1377-86. doi: 10.1038/leu.2008.96. Epub 2008 Apr 17.
- Dreger P, Schnaiter A, Zenz T, Bottcher S, Rossi M, Paschka P, Buhler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Dohner H, Stilgenbauer S. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood. 2013 Apr 18;121(16):3284-8. doi: 10.1182/blood-2012-11-469627. Epub 2013 Feb 22.
- Scheffold A, Jebaraj BMC, Jaramillo S, Tausch E, Steinbrecher D, Hahn M, Bottcher S, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P, Stilgenbauer S. Impact of telomere length on the outcome of allogeneic stem cell transplantation for poor-risk chronic lymphocytic leukaemia: results from the GCLLSG CLL3X trial. Br J Haematol. 2017 Oct;179(2):342-346. doi: 10.1111/bjh.14219. Epub 2016 Jul 8. No abstract available.
- Kramer I, Stilgenbauer S, Dietrich S, Bottcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood. 2017 Sep 21;130(12):1477-1480. doi: 10.1182/blood-2017-04-775841. Epub 2017 Jul 17. No abstract available.
연구 기록 날짜
연구 주요 날짜
연구 시작
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
추가 관련 MeSH 약관
- 심혈관 질환
- 혈관 질환
- 면역계 질환
- 조직학적 유형에 따른 신생물
- 신생물
- 림프 증식 장애
- 림프계 질환
- 면역증식성 장애
- 혈액 질환
- 출혈성 장애
- 지혈 장애
- 파라단백혈증
- 혈액 단백질 장애
- 신생물, 형질세포
- 백혈병, B세포
- 백혈병
- 발덴스트롬 마크로글로불린혈증
- 백혈병, 림프구성, 만성, B세포
- 백혈병, 림프
- 약물의 생리적 효과
- 약리작용의 분자기전
- 항감염제
- 핵산 합성 억제제
- 효소 억제제
- 항류마티스제
- 항대사물질, 항종양
- 항대사물질
- 항종양제
- 면역억제제
- 면역학적 요인
- 항종양제, 알킬화제
- 알킬화제
- 골수 파괴 작용제
- 항종양제, 면역학적
- 피부과 약제
- 항균제
- 항생제, 항종양제
- 항진균제
- 생식 조절제
- 항결핵제
- 낙태약제, 비스테로이드성
- 낙태 에이전트
- 엽산 길항제
- 항생제, 항결핵
- 칼시뉴린 억제제
- 사이클로포스파마이드
- 리툭시맙
- 플루다라빈
- 플루다라빈 포스페이트
- 메토트렉세이트
- 미코페놀산
- 부설판
- 항림프구 혈청
- 사이클로스포린
- 사이클로스포린
- 알렘투주맙
기타 연구 ID 번호
- CLL3X
- EU-20554
- MEDAC-FLUD.10/CLL
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
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