GvHD Prophylaxis With ATG-Fresenius S in Allogeneic Stem Cell Transplantation From Matched Unrelated Donors: A Randomized Phase III Multicenter Trial Comparing a Standard GvHD Prophylaxis With Cyclosporine A and Methotrexate With Additional Pretransplant ATG-Fresenius S
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 202
- 试验地点
- 1
- 主要终点
- Primary: Early treatment failure defined by the occurrence of severe acute GvHD (°III-°IV) or early mortality within 100 days post transplantation.
研究概览
简要总结
The study aim is to evaluate the influence of the anti-T-lymphocyte globulin ATG-Fresenius S given pre-transplant in addition to standard GvHD prophylaxis with cyclosporine A and a short course of methotrexate with respect to efficacy and safety.
详细描述
To assess the efficacy of ATG-FRESENIUS S in addition to standard therapy (cyclosporine A / methotrexate) with respect to early treatment failure defined by the occurrence of severe acute GvHD grade III-IV or early mortality within 100 days post transplantation compared to standard therapy alone.
All patients receive myeloablative therapy. Recommended regimens: For patients with ALL: fractionated TBI (8-12 Gy) plus cyclophosphamide (1-2 x 60 mg/kg) [etoposide/melfalan are also allowed]. For all other indications: either TBI (8-12 Gy) or busulfan (per os 14-16 mg/kg b.w. or equivalent for IV administration) plus cyclophosphamide (1-2 x 60 mg/kg) or thiotepa ≥ 15 mg/kg or BCNU ≥ 300 mg/m2.
Conditioning regimens may differ from centre to centre; each centre decides for constant (disease specific) regimen(s) throughout the whole study period.
Standard GvHD prophylaxis consists of cyclosporine A (target trough level ≥ 200 ng/ml starting from day -1 until day +100) and short course methotrexate (15 mg/m2 at day +1, 10 mg/m2 at days +3, +6 and +11).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participation of patients in simultaneous diagnostic and comprehensive therapeutical trials for certain entities is allowed.
- •Patients 18-60 years of age;
- •Patients suffering from one of the following diseases:
- •AML: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure);
- •ALL: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure);
- •MDS, if transplantation is medically indicated: RA (with poor risk factors as classified by the International Prognostic Scoring System of MDS), RARS, RAEB, RAEB-t, CMML;
- •CML: beyond 1st chronic phase (CP1): accelerated phase, blast crisis, chronic phase (CP2, CP3);
- •OMF, if transplantation is medically indicated: Osteomyelofibrosis;
- •Patients designated to undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem cell transplantation;
- •Patients with a HLA-A, -B (DNA-based, 2 digits), HLA-DRB1, -DQB1 (DNA-based 4 digits) matched (8 out of 8 alleles) unrelated donor; serological typing is not required
- •Patients with a Karnofsky Performance Score (KPS): > 60%;
- •Patients who underwent all obligatory screening examinations (special examinations within the last 4 weeks);
- •Patients who have given their written informed consent to participate in the study.
排除标准
- •Patients with significant cardiac (e.g. ejection fraction <50%), pulmonary (e.g. FEV1 <50%), renal (e.g. creatinine > 1.5 mg/dl), metabolic (e.g. bilirubin > 2.0 mg/dl) and/or CNS disease, currently uncontrolled by treatment, which may interfere with the completion of the study;
- •Patients with any bacterial, viral, or fungal infections not under adequate antimicrobial control;
- •Patients who are known to have serum hepatitis or who are carriers of the Hepatitis B surface antigen (HBs-Ag), or Hepatitis C antibody, or who are known to have a positive result to the test of HIV antibodies;
- •Patients with any additional concurrent or previous malignant disease;
- •Patients with known hypersensitivity to rabbit immunoglobulin antibodies in past patient history or with known allergy to any substance chemically related to the study medication;
- •Pregnant (β-HCG test) or lactating women;
- •Patients who formerly underwent transplantation including previous autologous transplants;
- •Patients who cannot communicate reliably with the investigator or who are not likely to cope with the requirements of the study.
研究组 & 干预措施
ATG-F
ATG-Fresenius S (20 mg/kg body weight at days -3 to -1 (total dose: 60 mg/kg)
cyclosporine A (target trough level > 200ng/ml (day -1 until day +100)
methotrexate: 15mg/m2 at day +1, 10mg/m2 at days +3, +6, and +11
干预措施: ATG-Fresenius S (Drug)
结局指标
主要结局
Primary: Early treatment failure defined by the occurrence of severe acute GvHD (°III-°IV) or early mortality within 100 days post transplantation.
时间窗: 100 days
次要结局
- Time to onset of acute GvHD, incidence and severity of infections until day +100, time to engraftment, incidence of cGvHD, disease free survival, relapse, death without relapse, overall survival, safety, tolerability.(24 months)