A Randomized Phase II Trial Comparing Treosulfan and Melphalan With Melphalan Alone as Conditioning Regimen for Autologous Stem Cell Transplantation (ASCT) in Myeloma Patients (TreoMel Trial)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Complete Remission (CR) Rate
研究概览
简要总结
Clinical trial investigating the chemotherapeutic compound treosulfan (Trecondi® Ideogen) in myeloma patients.
详细描述
Background and rationale:
Due to demographic changes, multiple myeloma with its preferential manifestation in the elderly population exerts increasing incidence worldwide. Since decades, autologous stem cell transplantation (ASCT) after high-dose chemotherapy (HDCT) with melphalan is the standard first-line consolidation option for patients with multiple myeloma considered fit for this approach. Nevertheless, subsequent relapse despite this intensive treatment is inevitable in most myeloma patients, emphasizing the unmet clinical need for improved conditioning strategies to further enhance the effect of HDCT treatment.
The Inselspital in Bern represents one of the largest European centers for autologous stem cell transplantation (ASCT) in myeloma, lymphoma and leukemia patients, and it is the largest center in Switzerland for ASCT, with more than 150 ASCT performed annually. In parallel, the transplant team at the Inselspital has a dedicated history of clinical trials aiming to further improve tolerance and efficacy of HDCT with ASCT.
In a previous randomized phase 2 study performed at the department of medical oncology of the Inselspital, the combination of the cytotoxic compound bendamustin in addition to the standard melphalan dose as a novel HDCT regimen before autologous transplantation in 120 myeloma patients has been explored and established. This approach was successful in terms of increased anti-myeloma efficacy, but the nephrotoxicity of high-dose bendamustin was relevant in a significant subset of patients. This fact, ultimately, led to the propose of a novel approach.
The present study aims to combine high-dose melphalan (Melphalan Ideogen) with treosulfan (Trecondi® Ideogen), a well established bifunctional alkylating agent. Treosulfan has a favorable toxicity profile, and it is used in patients with acute leukemias in the allogeneic transplant setting as a standard approach in an increasing number of centers. However, no study so far evaluated treosulfan combined with melphalan as high-dose chemotherapy in patients with multiple myeloma. Consequently, this approach is unique and novel in patients with multiple myeloma in the autologous transplant setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm B - TreoMel
Chemotherapy regime consisting of treosulfan on three days at 14 g/m2 followed by 200 mg/m2 melphalan given on two days at 100 mg/m2.
干预措施: Treosulfan (Drug)
Arm B - TreoMel
Chemotherapy regime consisting of treosulfan on three days at 14 g/m2 followed by 200 mg/m2 melphalan given on two days at 100 mg/m2.
干预措施: Melphalan (Drug)
Arm A - Mel
Chemotherapy regime consisting of 200 mg/m2 melphalan, split into two days à 100 mg/m2.
干预措施: Melphalan (Drug)
结局指标
主要结局
Complete Remission (CR) Rate
时间窗: 15 days after ASCT
Number of patients experiencing CR ( Myeloma assessment (serum free light chain ratio, M-gradient, IgG, IgA, IgM), Flow cytometry MRD, FISH analysis (plasma), Bone marrow (aspirate and biopsy) is performed only in patients fulfilling the criteria for CR. Bone marrow should be assessed at the end of the ASCT hospitalization)
次要结局
- Engraftment and hematologic recovery(15 days after ASCT)
- Overall survival(5 years)
- Adverse Events(15 days after ASCT)
- Infectious complications(15 days after ASCT)
- Renal toxicity(15 days after ASCT)
- Progression free survival(5 years)
- Hospitalisation duration(30 days)
- Minimal residual disease (MDR)(30 days)
- Pharmacodynamics of Treosulfan(Day -4)