Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk MDS or AML (PANOBEST)
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 62
- 试验地点
- 6
- 主要终点
- Maximum tolerated dose (MTD) of panobinostat
研究概览
简要总结
The study's primary objective is to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Panobinostat when administered within 150 days after hematopoietic stem cell transplantation (HSCT) and given in conjunction with standard immunosuppressive therapy after HSCT for patients with high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).
Secondary objectives are
- To determine safety and tolerability of panobinostat
- To determine overall and disease-free survival at 12 months after HSCT
- To evaluate immunoregulatory properties of panobinostat
- To evaluate patient-reported health-related quality of life (HRQL)
The hypothesis of this study is that panobinostat can be an effective drug in preventing relapse of MDS and AML patients with high-risk features after hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC-HSCT) while at the same time reducing graft-versus-host disease (GvHD) with preservation of graft-versus-leukemia (GvL) effect.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AML (except acute promyelocytic leukemia, AML M3) with high-risk features defined as one or more of the following criteria:
- •refractory to or relapsed after at least one cycle of standard chemotherapy
- •> 10% bone marrow blasts at day 15 of the first induction cycle
- •adverse risk cytogenetics including complex karyotype (≥ 3 abnormalities or abnormalities of chromosomes 3, 5 or 7) regardless of stage
- •secondary to MDS or radio-/chemotherapy or
- •MDS RAEB according to the WHO classification or intermediate-2 or high-risk according to IPSS or
- •Chronic myelomonocytic leukemia (CMML) with ≥ 5% bone marrow blasts and
- •Allogeneic HSCT with reduced intensity conditioning (see Section 15.1 for definition) performed within 60 - 150 days prior to study entry
- •Complete hematologic remission documented by bone marrow aspiration within 28 days prior to study entry
排除标准
- •Active acute GvHD overall grade 2 - 4
- •Prior treatment with a deacetylase (DAC) inhibitor
- •Patients with impaired cardiac function or other concurrent severe and/or uncontrolled medical conditions
- •Clinical symptoms suggesting central nervous system (CNS) leukemia
- •Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
研究组 & 干预措施
Panobinostat Arm A
干预措施: Panobinostat (Drug)
Panobinostat Arm B
干预措施: Panobinostat (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of panobinostat
时间窗: after 28 days of administration
Dose-limiting toxicity (MTD) of Panobinostat
时间窗: after 28 days of administration
次要结局
- patient-reported health-related quality of life(after 3 months of administration and one month after last intake of study drug)
- Cumulative incidence of hematologic relapse and death(one year after HSCT)
- Cumulative incidence of extensive chronic GvHD(one year after HSCT)
- Duration of complete donor chimerism(patients will be followed for up to 2 years depending on the duration of study participation)
- Cumulative incidence of severe acute GvHD(one year after HSCT)
- Reconstitution of the immune system as measured by changes in numbers, ratio, phenotype and activation state of peripheral blood cell populations during panobinostat therapy(patients will be followed for up to 2 years depending on the duration of study participation)
- Time to complete donor chimerism(patients will be followed for up to 2 years depending on the duration of study participation)
研究者
Gesine Bug
Senior physician hematology
Johann Wolfgang Goethe University Hospital