Efficacy of 6x R-CHOP Followed by Myeloablative Radiochemotherapy and Autologous Stem Cell Transplantation vs. 3 x (R-CHOP/R-DHAP) Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 360
- 试验地点
- 3
- 主要终点
- time to treatment failure after start of therapy
研究概览
简要总结
The aim of this study is to determine whether alternating courses of cyclophosphamide, doxorubicin, vincristine, prednisone/dexamethasone, cytarabine, cisplatin (CHOP/DHAP) plus rituximab followed by total body irradiation [TBI]/high dose cytarabine [ARA-C]/melphalan-peripheral blood stem cell transplantation (TAM-PBSCT) can improve the time to treatment failure compared to CHOP plus rituximab followed by standard PBSCT (dexamethasone, carmustine, cytarabine, etoposide, and melphalan [Dexa-BEAM]/TBI/high dose cyclophosphamide) in patients with untreated mantle cell lymphoma.
详细描述
Recently, a prospective randomized intergroup trial of the European MCL Network has shown that a myeloablative radio-chemotherapy followed by autologous stem cell transplantation (PBSCT) improves event-free survival (EFS) when compared to a interferon alpha maintenance therapy after a CHOP-like induction. However, the CR rate after the CHOP induction was still low (<20%). Thus, several studies have been conducted to increase the CR rate of induction therapy to further improve event-free and overall survival. Two recent phase II trials suggest that induction regimens containing high dose Ara-C may significantly improve the CR rate up to 80%. In addition, a number of studies provide evidence that the humanized anti-CD20 antibody Rituximab may induce significant responses in relapsed MCL. A prospective randomized study of the GLSG demonstrated that a combined immuno-chemotherapy (CHOP plus Rituximab) induces a significantly higher response rate than CHOP alone.
The aim of this study is the comparison of the current standard (R-CHOP followed by myeloablative radio-chemotherapy and subsequent blood stem cell transplantation) to a new alternating induction regimen containing high dose Ara-C (R-CHOP/DHAP) followed by a high dose ARA-C containing myeloablative radio-chemotherapy and PBSCT.
This study will be performed as a prospective, randomized, open-label multicenter phase III trial. All patients will be initial randomized for standard treatment versus experimental treatment.
REFERENCE ARM:
The induction therapy consists of 6 cycles of a CHOP chemotherapy in combination with Rituximab. If the mantle cell lymphoma is progressive after 4 cycles of chemotherapy, patients will be taken off study. Patients achieving at least a partial remission after 6 cycles R-CHOP will proceed to intensified consolidation (Dexa-BEAM) with stem cell collection and subsequent myelo-ablative radio-chemotherapy (TBI/High Dose Cyclophosphamide) with autologous stem cells transplantation
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven diagnosis of mantle cell lymphoma (World Health Organization [WHO] classification)
- •Clinical stage II - IV (Ann Arbor)
- •Previously untreated patients
- •Age 18 - 65 years
- •WHO performance < 2
- •Measurable disease (also: patients with isolated bone marrow involvement)
- •Informed consent according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use/European Union Good Clinical Practice (ICH/EU GCP) and national/local regulations
排除标准
- •Age > 65 years
- •WHO performance status > 2
- •Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
- •Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or interferon
- •Serious disease interfering with a regular therapy according to the study protocol:
- •cardiac (e.g. manifest heart failure, coronary heart disease, uncontrolled hypertension)
- •pulmonary (e.g. chronic lung disease with hypoxemia)
- •endocrine (e.g. severe, not sufficiently controlled diabetes mellitus)
- •renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal value and/or creatinine clearance < 50 ml/min)
- •impairment of liver function (unless caused by the lymphoma): transaminases > 3x normal or bilirubin > 2,0 mg/dl
- •Patients with unresolved hepatitis B or C infection or known HIV infection
- •Prior organ, bone marrow or peripheral blood stem cell transplantation
- •Concomitant or previous malignancies within the last 5 years other than basal cell skin cancer or in situ uterine cervix cancer.
- •Pregnancy or lactation
- •Any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule
研究组 & 干预措施
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: Vincristine (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: Prednisone (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: BCNU (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: Doxorubicin (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: Rituximab (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: Cyclophosphamide (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: Melphalan (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: Etoposide (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: G-CSF (Drug)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: stem cell harvest (Procedure)
1
induction: R-CHOP consoldiation : TBI/Cyclo
干预措施: total body irradiation (Procedure)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Rituximab (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Cyclophosphamide (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Doxorubicin (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Vincristine (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Prednisone (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Cisplatinum (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Ara-C (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Dexamethasone (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: Melphalan (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: G-CSF (Drug)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: stem cell harvest (Procedure)
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
干预措施: total body irradiation (Procedure)
结局指标
主要结局
time to treatment failure after start of therapy
次要结局
- complete remission (CR) rate
- overall survival
- progression-free survival
- adverse events
- serious infectious complications