Sequential Trial on Reduced Intensity Conditioning (RIC) Allogeneic Transplantation (EMN-alloRIC)
European Myeloma Network Sequential Phase I / Phase II Trial on RIC Allogeneic Transplantation: an Optimized Program for High Risk Relapsed Patients
The aim of the current study is to improve the outcome of patients with hematologic malignancies (in a phase I trial) and more specifically multiple myeloma (in a phase II trial) by 2 interventions: reduce the risk of graft-versus-host disease (GVHD) and improve the efficacy of the procedure decreasing the risk of relapses after transplant.
Currently, the standard approach used in most centers to prevent graft-versus-host disease after allogeneic transplantation is based on the combination of a calcineurin inhibitor (cyclosporine or tacrolimus) plus a short course of methotrexate. Unfortunately, this strategy is far from ideal, since the risk of acute GVHD is in the range of 30-40% among patients receiving a matched related donor transplantation and even higher among patients receiving transplantation from an unrelated donor while the incidence of chronic GVHD is 60-70% among patients receiving peripheral blood progenitor cells from either a related or unrelated donor.
As far as the patients with multiple myeloma (MM) is concerned, although the development of new drugs has markedly changed the outcome and management of these patients, allogeneic transplantation so far appears to be the only curative option, especially among those patients relapsing after first line treatment. Nevertheless, still new strategies within the allogeneic transplant setting are needed to improve its results.
Relapses may occur either extramedullary (very common in this setting) or systemic. In order to reduce the risk of systemic relapses the investigators will use maintenance therapy with Lenalidomide (Len) which, together with bortezomib (Bz) should contribute to eradicate minimal residual disease (MRD). In case the patient do not obtain complete remission or near complete remission after transplant, in addition to the maintenance therapy, the investigators will use four intensification cycles with VRD (Bz-Len-Dexamethasone).
In summary, the goal is to optimize the efficacy of allogeneic transplantation by two interventions: one focused on reducing the risk of relapse and the other on reducing the incidence of GVHD.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Würzburg,、德国
- Medizinische Klinik and Poliklinik II, University Hospital
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Torino、意大利
- S Giovanni Battista Hospital
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Udine、意大利
- Azienda Ospedaliera Universitaria di Udine
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Stockholm、瑞典
- Karolinska University Hospital, Huddinge
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Barcelona,、西班牙
- Hospital Clinic i Provincial,
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Barcelona,、西班牙
- Hospital Santa Creu I Sant Pau,
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Madrid、西班牙、28034
- Hospital Universitario Ramon y Cajal
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Madrid、西班牙
- Hospital Gregorio Marañón,
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Salamanca,、西班牙
- Hospital Clinico Universitario Salamanca,
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Sevilla、西班牙
- Hospital Universitario Virgen del Rocío,
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Phase I: For the first 10 patients:
- Patients with any haematological malignancy in > CR1 (first complete remission)
- Suitable related donor human leukocyte antigen (HLA)identical
- Age > 18 and < 70 years
For the 10 subsequent patients:
- Patients with any haematological malignancy candidates to receive an allogeneic transplant
- Suitable related or unrelated donor (a maximum of 1 mismatched is allowed)
- Age > 18 and < 70 years phase II trial:
- High-risk multiple myeloma patients at first relapse / second complete remission candidates to receive an allogeneic transplantation
- Age:> 18 < 70 years.
- Suitable donor, related or unrelated (a maximum of 1 mismatched is allowed)
- Measurable disease
- High risk first relapse is defined as:
- First early relapse after Autologous Stem Cell Transplant (ASCT)< 24 months
- First late relapses in case the patient does not achieve CR after second ASCT
- First relapse in patients with poor cytogenetic features
- All subjects must be able to comply with the Lenalidomide Pregnancy Prevention Risk Management Plan.
Exclusion Criteria:
Any of the following:
Prior severe comorbidity such as:
- Heart failure or previous infarction
- Uncontrolled Hypertension
- Arrhythmia
- Cirrhosis
- Peripheral neuropathy >Grade 2, 14 days prior to inclusion
- Psychiatric disease
- Prior history of other neoplasia except for carcinoma in situ in the last 10 years
- Hypersensitivity to Bz, Boric acid mannitol.
- Patients unable to use appropriate contraceptive methods
- Patients who have received an investigational drug 30 days prior to inclusion
- Positive human immunodeficiency virus (HIV) or active viral hepatitis
- Patients with pericardial disease
- Patients with acute diffuse infiltrative pulmonary disease
- Patients not willing to comply with the Lenalidomide Pregnancy Prevention Risk Management Plan
- Patients not willing to receive thromboprophylaxis during the consolidation phase will not be eligible.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Bortezomib + Lenalidomide
After conditioning treatment and graft versus host disease prophylaxis with Bz 1.3 mg/m2 on days +1, +4 and +7 plus sirolimus/rapamycin at a dose of 6 mg po on day -5 and then 4 mg per day in order to maintain serum levels in the range of 6-12 ng /mL, a maintenance therapy with Bz 1.3 mg/m2 on days 1, 8 and 15 in cycles of 56 days up to 6 cycles post-transplant and on day +180 Len will be started at a dose of 5 mg and will be maintained until relapse.
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Bz 1.3 mg/m2 on days +1, +4 and +7.
Maintenance therapy and dose reduction pre-specified.
其他名称：
Len at a dose of 6 mg po on day -5 and then 4 mg per day in order to maintain serum levels in the range of 6-12 ng /mL. Maintenance therapy and dose reduction pre-specified.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Phase I trial: Safety of Len + Bz in patients with hematologic malignancies Phase II trial: Safety and efficacy of an optimized strategy of allogeneic transplantation in multiple myeloma undergoing allogeneic transplantation.
大体时间：Up to one year after transplant
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For phase I trial: safety of Len + Bz. The phase I trial safety criteria will be evaluated in terms of (1) engraftment defined as > 500 granulocytes / microL and > 20.000 platelets / microL x 3 consecutive days will be required for 9/10 patients, (2) incidence of neuropathy grades 3-4 attributed to Bz > 20% (3) incidence of gastrointestinal toxicity attributed to Bz > 20%. For phase II trial: safety evaluated through adverse events and toxicity and efficacy evaluated as reduction of relapse rate as defined by the EBMT criteria. |
Up to one year after transplant
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Incidence of GVHD with this combination (phase I and II)
大体时间：Up to one year after transplant
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Evaluation of a novel combination of Bz plus Len to prevent GVHD after allogeneic transplantation in patients with haematologic malignancies/MM
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Up to one year after transplant
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Phase II: response and relapse rate of this approach
大体时间：Up to one year after transplant
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Reduction of relapse rate as defined by the EBMT (European Group for Blood, and Marrow Transplant)criteria.
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Up to one year after transplant
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Phase II: safety of the procedure
大体时间：Up to one year after transplant
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For all patients safety will be assessed by the reporting of adverse events starting with the first study-related procedure and up to 30 days after the treatment period.
The severity of adverse events will be assessed using National Cancer Institute (NCI) common toxicity criteria (CTC).
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Up to one year after transplant
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Evaluate the efficacy on survival
大体时间：Up to one year after transplant
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Evaluate the efficacy of the procedure in terms of event free and overall survival
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Up to one year after transplant
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Efficacy of positron emission tomography (PET scan)and local radiotherapy
大体时间：Up to one year after transplant
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Analyze the prognostic value and efficacy of imaging studies using PET scan and local radiotherapy in involved fields prior to or after (> 100 days) conditioning
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Up to one year after transplant
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合作者和调查者
调查人员
- 首席研究员：Jose-Antonio Perez-Simon, MD-PhD、University Hospital Virgen del Rocio
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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