NCT02663752终止2 期
A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy in Hematological Centers in Belgium Using Gene Expressing Profiling From Baseline Bone Marrow.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders'
研究概览
简要总结
Several previous studies (clinical and non-clinical) hypothesize that treatment with deferasirox causes a hematological improvement in transfused patients with low and intermediate-1 risk myelodysplastic syndrome. The purpose of this study was to assess the presence of genetic biomarkers predictive for hematologic response by the use of gene expression profiling of bone marrow aspirates obtained from MDS patients with or without hematological response.
详细描述
This trial was terminated due to low enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- •Written informed consent obtained prior to any other study procedure,
- •Males or females ≥ 18 years of age,
- •MDS according to WHO criteria lasting ≥ 14 weeks at the time of screening, IPSS score <1.5 (low and intermediate-1 risk patients) at the time of screening using the IPSS score of 1997
- •Treatment with deferasirox:
- •Only for the responder group: Treatment with deferasirox for prevention or treatment of IOL for at least 14 weeks before screening.
- •Only for the non-responder group: Treatment with deferasirox for at least 9 months for prevention or treatment of IOL before screening to exclude patients with a late hematological response.
- •Only for responder-group: Patient with hematological response defined according to the IWG criteria of 2006 which must last at least 8 weeks, confirmed by the scientific advisory committee. In case a hematological response is identified retrospectively, the confirmation will be based on the last available blood result showing hematological response according to the IWG criteria of
- •In this case, an archived bone marrow sample at the moment of response has to be available in order to be eligible. This archived bone marrow had to be taken at the moment when hematological response was present for at least 8 weeks and was still ongoing at the moment of sampling, according to the IWG criteria of 2006 in order to be eligible. When a bone marrow sample was taken after the hematological response had already disappeared, the sample is not eligible for further analysis.
- •Only for non-responder group: confirmation by the scientific advisory committee that patient is eligible based on matched-pairing and confirmation of no hematological response. Minimal requirements for matched pairing include age, sex, IPSS score, hemoglobin level, transfusion need at baseline, treatment duration with deferasirox and time since MDS diagnosis. Pairing can be extended according to level of leukopenia, thrombocytopenia, serum ferritin level at baseline, comorbidities and transfusion history. More details about pairing are described in the protocol. In case a non-responder is identified retrospectively and an archival bone marrow is available at that documented time of non-response, this can be used for further analysis. In that case, an interval of 4 weeks between blood sampling for documentation of non-response and bone marrow sampling is allowed.
- •Bone marrow aspirate/RNA taken at the time of MDS diagnosis (at baseline) retrievable from patient's hospital. This should be checked by the treating hematologist/oncologist before referring the patient for potential inclusion to the study. This aspirate/RNA has to be preserved under the right circumstances in order to ensure the quality of the RNA. The sample most be frozen viably, meaning controlled rate freezing and addition of a protector dimethyl sulfoxide DMSO and preserved in -80°C. Preservation of cells that are lysed in a lysis buffer upon arrival in the lab, and stored at -20°C until RNA-extraction are also useful for this study.
排除标准
- •Known concomitant presence of anemia due to iron, B12 or folate deficiencies, auto-immune or hereditary hemolysis, gastro-intestinal bleeding or medication induced anemia at the time of screening,
- •Known infection with viral hepatitis B (HBV) or viral hepatitis C (HCV) defined as the presence in blood of HBV antigens in absence of HB antibodies, or presence of HCV antibodies at the time of screening,
- •Known history of positivity to human immunodeficiency virus (HIV) measured by enzyme-linked immunosorbent assay (ELISA) or western blot at the time of screening,
- •Patient participating in another clinical trial or receiving any investigational drug at the time of screening within 1 month prior to study inclusion
- •History of other malignancy within the last five years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ
- •Concomitant treatment with other drugs known or suspected to elicit hematological response. (azacitidine, hematopoietic growth factors, granulocyte colony stimulating factors, valproate, lenalidomide, thalidomide, ATG, cyclosporine, arsenic trioxide).When patients are still receiving red blood cell transfusions, patients are still eligible for study inclusion as long as they meet the IWG criteria of 2006
- •Female patients who are pregnant or breast feeding
研究组 & 干预措施
Deferasirox
Other
All patients are already on commercial deferasirox before entering the study.
干预措施: Bone marrow aspirate (Procedure)
Deferasirox
Other
All patients are already on commercial deferasirox before entering the study.
干预措施: Deferasirox (Drug)
结局指标
主要结局
Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders'
时间窗: 18 months
Using next-generation sequencing, gene expression profiling in responder and non-responder patients were to be performed on existing bone marrow aspirate samples. Gene transcription were then to be compared between the two groups and the fold increase/decrease in differentially expressed genes were to be calculated.
次要结局
- Time to Response(18 months)
- Changes in Serum Ferritin Levels(Baseline, 18 months)
- Deferasirox Dose Used(18 months)
- Changes in Serum Transferrin Levels(Baseline, 18 months)
- Changes in Transferrin Saturation Levels(Baseline, 18 months)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
2 期
Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.Low and Int 1-risk Myelodysplastic SyndromeNCT01868477Novartis Pharmaceuticals28
终止
2 期
Deferasirox in Treating Patients With Very Low, Low, or Intermediate-Risk Red Blood Cell Transfusion Dependent Anemia or Myelodysplastic SyndromeAnemiaMyelodysplastic SyndromeNCT02943668Fred Hutchinson Cancer Center2
进行中（未招募）
不适用
Phase I study to examine the effect of deferasirox on renal hemodynamics in β-thalassemia patients with transfusional iron overload - NDMedDRA version: 6.1Level: HLGTClassification code 10022958thalassemiaEUCTR2006-006838-17-ITOVARTIS FARMA8
已完成
2 期
Efficacy and Safety of Deferasirox in Patients With Chronic Anemia and Transfusional HemosiderosisChronic AnemiaTransfusional HemosiderosisNCT00631163Novartis Pharmaceuticals102
已完成
2 期
Extension Study of Iron Chelation Therapy With Deferasirox in β-thalassemia and Rare Chronic Anemia PatientsHemosiderosisAnemiaNCT00303329Novartis Pharmaceuticals184