NCT01883362已完成2 期
A Phase II, Randomized Trial of Standard of Care, With or Without Midostaruin to Prevent Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients With FLT3-ITD Mutated Acute Myeloid Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 19
- 主要终点
- Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis
研究概览
简要总结
To determine if the addition of midostaurin (PKC412) to Standard of Care (SOC) therapy reduces relapse in FLT3-ITD mutated AML patients receiving an allogenetic hematopoietic stem cell transplant,
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients between 18 and 70 years of age
- •Patients with ECOG Performance Status of ≤ 2
- •Patients with a documented unequivocal diagnosis of AML according to WHO 2008 classification (>20% blasts in the bone marrow), excluding M3 (acute promyelocytic leukemia).
- •Patients with a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation)
- •Patients who undersent allogeneic HSCT in CR1 from a matched related or matched unrelated donor. All of the following criteria had to be met: HLA typing to include available 8/8 or 7/8 allele HLA matched donor (at A,B,C, DRB1) Single allelic mismatch allowed
- •Patients who had received a conditioning regimen which included one of the following:
- •Busulfan/Fludarabine (Bu/Flu) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Fludarabine (120-180 mg/m2) Fludarabine / Melphalan (Flu/Mel) Fludarabine (120-180 mg/m2) Melphalan (≤ 150 mg/m2) Busulfan/Cyclophosphamide (Bu/Cy) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Cyclophosphamide (120 mg/kg) Cyclophosphamide/Total Body Irradiation (Cy/TBI) Cyclophosphamide (120 mg/kg) TBI (1200-1420 cGy)
- •Recovery of counts by day 42 and was able to start midostaurin by day 60 post-HSCT (first dose of midostaurin to start no earlier than 28 days post-HSCT); ANC >1000µL, platelets ≥20,000 without platelet transfusion
排除标准
- •Patients eligible for this study must not have met any of the following criteria:
- •Patients who failed prior attempts at allogeneic HSCT
- •Patients who had received an autologous transplant
- •Patients with Acute GVHD Grade III-IV
- •Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis.
- •Impaired cardiac function including any of the following:
- •Screening ECG with a QTc > 450 msec. If QTc > 450 and electrolytes were not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc.
- •Patients with congenital long QT syndrome
- •History or presence of sustained ventricular tachycardia
- •Any history of ventricular fibrillation or torsades de pointes
- •Bradycardia defined as HR. < 50 bpm
- •Right bundle branch block + left anterior hemiblock (bifascicular block)
- •Patients with myocardial infarction or unstable angina < 6 months prior to starting study
- •Congestive Heart Failure NY Heart Association class III or IV
- •Patients with an ejection fraction < 45% assessed by MUGA or ---ECHO within 28 days prior to starting study cycle 1 (of midostaurin or control group)
- •Patients with any pulmonary infiltrate including those suspected to be of infectious origin (unless resolves to ≤ Grade 1 within screening timeframe)
- •Patient required treatment with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers other than those required for GVH or infection prophylaxis or treatment
- •Pregnant or nursing (lactating) women, or women of child-bearing potential, must have used highly effective methods of contraception during dosing and for 30 days after treatment completion
研究组 & 干预措施
Standard of Care
Active Comparator
Patients received standard of care alone in the post SCT setting
干预措施: Standard of Care (Other)
Standard of Care with Midostaurin
Experimental
Patients received standard of care in the post stem cell transplant (SCT) setting in addition to Midostaurin 50mg twice a day for 12 months (cycles).
干预措施: Midostaurin (Drug)
结局指标
主要结局
Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis
时间窗: date of transplant up to 18 months
Relapse-free survival assesses the clinical benefit of remaining in remission free from relapse or death due to the disease. It was defined as the time from transplant to relapse or death due to the disease. Relapse following complete response was defined as reappearance of leukemic blasts in the peripheral blood or finding more than 5% blasts in the bone marrow.
次要结局
- Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis(date of transplant up to 24 months)
- Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis(date of transplant up to 24 months)
- Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels(Pre-dose on days 1 and 15 of Cycle 1, on day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis(Randomization to 18 months)
- Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis(date of transplant up to 24 months)
- FLT3-ITD Mutation Status Centrally in Archived Material From Diagnosis (if Available) Including Mutant:Wild Type Ratio.(up to 24 months from date of transplannt or at study completion)
- Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis(date of transplant up to 24 months)
研究者
研究点 (19)
Loading locations...
相似试验
进行中（未招募）
2 期
A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AMLFLT3-mutated Acute Myeloid LeukemiaNCT03591510Novartis Pharmaceuticals22
已完成
2 期
Phase 2 Midostaurin in Aggressive Systemic Mastocytosis and Mast Cell LeukemiaSystemic Mastocytosis, Aggressive (ASM)Leukemia, Mast CellHematological Non-mast Cell Lineage Disease (AHNMD)NCT00233454Jason Robert Gotlib26
已完成
2 期
Efficacy, Safety, Tolerability, Pharmacokinetics of Sotrastaurin-tacrolimus vs. Mycophenolic Acid-tacrolimus in de Novo Liver Transplant PatientsLiver TransplantationNCT01128335Novartis Pharmaceuticals200
No Longer Available
不适用
Midostaurin Access Program for Newly Diagnosed FLT3 (ITD or TKD) Mutated AML Adult Patients Eligible for Standard Induction and Consolidation ChemotherapyAcute Myeloid Leukemia (AML) WithFLT3 Mutation, Internal Tandem Duplication (ITD) or Tyrosine Kinase Domain (TKD)NCT02624570Novartis Pharmaceuticals
进行中（未招募）
1 期
Phase-II study evaluating midostaurin in induction, consolidation andmaintenance therapy also after allogeneic blood stem cell transplantationin patients with newly diagnosed acute myeloid leukemia exhibiting a FLT3 internal tandem duplication AMLSG 16-10EUCTR2011-003168-63-DEniversity Hospital Ulm440