NCT00598624Unknown2 期
Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Haematological Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 入组人数
- 175
- 试验地点
- 12
- 主要终点
- Efficacy: Evaluation of engraftment
研究概览
简要总结
This is a multicentric, non-randomized, non-controlled open-label phase II trial to evaluate the safety and efficacy of treosulfan in a combination regimen with fludarabine as conditioning therapy prior to allogeneic stem cell transplantation (SCT) in patients with haematological malignancies.
The aim is to demonstrate a clinical benefit compared with historical data on intravenous busulfan (BusulfexTM, BusilvexTM), the only drug so far registered in the indication conditioning before allogeneic stem cell transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with haematological malignancies, according to WHO classification, such as:
- •acute myeloid leukaemia -AML- in CR1 except "low-risk cases" defined by t(15;17), t(8;21), inv 16 or normal cytogenetics at diagnosis with FLT3-ITD negative and NPM-1 positive, with no high risk clinical criteria
- •any AML beyond CR1
- •acute lymphoblast leukaemia -ALL- in CR1 only if at "high risk" defined by cytogenetics as t(9;22), t(4;11) or for persistence of minimal residual disease (MRD)
- •any ALL beyond CR1
- •chronic myeloid leukaemia -CML- in chronic phase (CP) or accelerated phase (AP) intolerant/not responsive to TK-inhibitors
- •myeloproliferative disorders -MPD-
- •myelodysplastic syndrome -MDS- with intermediate or high risk International Prognostic Scoring System (IPSS)
- •diffuse large cell lymphoma -DLCL- with a chemosensitive relapse or beyond CR1
- •lymphoblastic and Burkitt lymphoma with a chemosensitive relapse or beyond CR1
- •mantle cell lymphoma -MCL- with a chemosensitive relapse or beyond CR1
- •follicular lymphoma -FCL- with a chemosensitive relapse or beyond CR2
- •Hodgkin lymphoma -HD- with a chemosensitive relapse or beyond CR1
- •chronic lymphocytic leukaemia -CLL- at "poor risk" in CR1 or with a chemosensitive relapse
- •CLL relapsing after high dose chemotherapy
- •T-cell non Hodgkin lymphoma -T-NHL- in CR1 or beyond
- •multiple myeloma -MM- at high risk for cytogenetics or ISS stage 3 in CR1 following high dose chemotherapy
- •MM at any relapse/progression except refractory disease
- •Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD)
- •HLA-identity defined by the following markers: A, B, DRB1, DQB1 or a single or double Cord Blood unit (CB) with at least a 4 out of 6 HLA-matching by the following markers: A, B and DRB.
- •A) identity between the 2 CB units and the recipient;
- •B) Two identical CB units with one or two mismatches with the recipient;
- •C) Two CB units with one mismatch between them and two mismatches with the recipient. We will prefer mismatches either for class I or for class II antigens; we will avoid mismatches concerning both classes I and II together.
- •Target graft size (unmanipulated, preferably not cryopreserved)
- •bone marrow: 2 to 10 x 106 CD34+ cells/kg BW recipient or > 2 x 108 nucleated cells/kg BW recipient or
- •peripheral blood: 4 to 10 x 106 CD34+ cells/kg BW recipient
- •Age > 18 and < 70 years
- •Karnofsky Index > 80 %
- •Adequate contraception in female patients of child-bearing potential
- •Written informed consent
排除标准
- •Secondary malignancies
- •Previous allogeneic transplantation
- •Hematopoietic cell transplantation-specific comorbidity index > 4 (HCT-CI Sorror et al, Appendix M)
- •Known and manifested malignant involvement of the CNS
- •Active infectious disease
- •HIV- positivity or active hepatitis infection
- •Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)
- •Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
- •Pleural effusion or ascites > 1.0 L
- •Pregnancy or lactation
- •Known hypersensitivity to treosulfan and/or fludarabine
- •Participation in another experimental drug trial within 4 weeks before day -6
- •Non-co-operative behaviour or non-compliance
- •Psychiatric diseases or conditions that might impair the ability to give informed consent
研究组 & 干预措施
A
Experimental
干预措施: Treosulfan IV (Drug)
结局指标
主要结局
Efficacy: Evaluation of engraftment
时间窗: 28 days
Safety: Evaluation of the incidence of CTC grade 3 and 4 adverse events
时间窗: between day -6 and day +28
次要结局
- Efficacy: Evaluation of disease free survival (DFS)(1 year)
- Efficacy: Evaluation of overall survival (OS)(1 year)
- Efficacy: Evaluation of relapse incidence (RI)(1 year)
- Efficacy: Documentation of donor chimerism(on day +28, +56 and +100)
- Safety: Evaluation of incidence of non-relapse mortality (NRM)(on day +28 and day +100)
- Safety: cumulative incidence of NRM(1 year)
- Safety: Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD)(1 year)
- Safety: EBV reactivation(1 year)
研究者
研究点 (12)
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