A Phase II Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Myeloablative Fludarabine/Busulfan and Post-Transplant Cyclophosphamide (PTCY) for Fully Human Leukocyte Antigen (HLA)-Matched and Partially-HLA Mismatched Allogeneic Transplantation Patients With High-Risk AML, CML, and MDS
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 2
- 主要终点
- GVHD-Free Relapse-Free Survival after Stem Cell Transplant
研究概览
简要总结
The study is a Phase II clinical trial. Patients will receive intensity-modulated total marrow irradiation (TMI) at a dose of 9 Gray (Gy) with standard myeloablative fludarabine intravenous (IV) and targeted busulfan (FluBu4) conditioning prior to allogeneic hematopoietic stem cell transplant (HSCT). Graft-versus-host disease (GVHD) prophylaxis will include Cyclophosphamide on Day +3 and +4, tacrolimus, and mycophenolate mofetil.
详细描述
Patients will receive the following conditioning regimen: fludarabine 40 mg/m2 IV piggyback daily, from day -5 (5 days before stem cell infusion) through Day -2, IV busulfan targeting a 4800 μM/min/ day, from day -5 through day -2. In addition to the above chemotherapy, all patients will receive TMI at a dose of 3Gy on days -3, -2, and -1. On day 0, the stem cell product will be infused according to BMT (Bone Marrow Transplant) unit policy. Graft versus host disease (GVHD) prophylaxis will consist of the administration of Cyclophosphamide 50 mg/Kg on days 3 and 4 and mycophenolate mofetil combined with tacrolimus. Post-transplant evaluation will be done per standard care with study data collected at days 30, 60, 90, 180, 365, and 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Age 18-65 years.
- •2. Patients with CML, AML, or MDS who meet one of the following criteria: 2a. Relapsed or refractory AML (including AML in CR2) 2b. Poor-risk AML in first remission, with remission defined as <5% bone marrow blasts morphologically:
- •AML arising from MDS, a myeloproliferative disorder, or secondary AML
- •Poor risk molecular features according to Leukemia Net including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
- •Poor-risk cytogenetics: Monosomal karyotype, complex karyotype (> 3 abnormalities), inv (3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or
- •2c. Primary refractory disease 2d. MDS with at least one of the following poor-risk features:
- •Poor-risk cytogenetics including 3q abnormalities, 7/7q minus or complex cytogenetics (>3 abnormalities).
- •Current or previous INT-2 or high IPSS score.
- •Treatment-related MDS.
- •MDS diagnosed before the age of 21 years.
- •Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy.
- •Life-threatening cytopenias, including those requiring regular PRBC or platelet transfusions. 2e. CML with a history of accelerated or blast phase.
排除标准
- •1. Presence of significant co-morbidity as shown by:
- •1a. Left ventricular ejection fraction < 50%
- •2b. Creatinine clearance <30ml/min.
- •3c. Bilirubin > 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST > 5 x ULN.
- •4d. FEV1 and FVC < 50% of predicted or DLCO <50% of predicted once corrected for anemia.
- •5e. Karnofsky score <70
- •6f. Active viral hepatitis or HIV infection.
- •7g. Cirrhosis.
- •2. Pregnancy or breast feeding
- •3. Patients unable to sign informed consent.
- •4. Patients previously received radiation to >20% of bone marrow-containing areas.
研究组 & 干预措施
Treatment Regimen
Days -5 through -2: Fludarabine 40 mg/m2 IVPB daily and Busulfan targeting AUC 4800μM/min daily Day -3 through -1: Intensity modulated total marrow irradiation (9Gy fractionated) Day 0: Infuse peripheral blood mobilized stem cells Days +3 and +4: Cyclophosphamide 50 mg/kg/day Day 5: Mycophenolate mofetil and Tacrolimus (dose adjustment dependent on trough level) Day 30: Follow up Day 60: Follow up Day 90: Follow up Day 180: Follow up
- year: Follow up
- year: Follow up
干预措施: Intensity modulated total marrow irradiation (Radiation)
Treatment Regimen
Days -5 through -2: Fludarabine 40 mg/m2 IVPB daily and Busulfan targeting AUC 4800μM/min daily Day -3 through -1: Intensity modulated total marrow irradiation (9Gy fractionated) Day 0: Infuse peripheral blood mobilized stem cells Days +3 and +4: Cyclophosphamide 50 mg/kg/day Day 5: Mycophenolate mofetil and Tacrolimus (dose adjustment dependent on trough level) Day 30: Follow up Day 60: Follow up Day 90: Follow up Day 180: Follow up
- year: Follow up
- year: Follow up
干预措施: Cyclophosphamide (CTX) (Drug)
Treatment Regimen
Days -5 through -2: Fludarabine 40 mg/m2 IVPB daily and Busulfan targeting AUC 4800μM/min daily Day -3 through -1: Intensity modulated total marrow irradiation (9Gy fractionated) Day 0: Infuse peripheral blood mobilized stem cells Days +3 and +4: Cyclophosphamide 50 mg/kg/day Day 5: Mycophenolate mofetil and Tacrolimus (dose adjustment dependent on trough level) Day 30: Follow up Day 60: Follow up Day 90: Follow up Day 180: Follow up
- year: Follow up
- year: Follow up
干预措施: Fludarabine (Fludara) (Drug)
Treatment Regimen
Days -5 through -2: Fludarabine 40 mg/m2 IVPB daily and Busulfan targeting AUC 4800μM/min daily Day -3 through -1: Intensity modulated total marrow irradiation (9Gy fractionated) Day 0: Infuse peripheral blood mobilized stem cells Days +3 and +4: Cyclophosphamide 50 mg/kg/day Day 5: Mycophenolate mofetil and Tacrolimus (dose adjustment dependent on trough level) Day 30: Follow up Day 60: Follow up Day 90: Follow up Day 180: Follow up
- year: Follow up
- year: Follow up
干预措施: Busulfan (conditioning for ALLO Transplant) (Drug)
结局指标
主要结局
GVHD-Free Relapse-Free Survival after Stem Cell Transplant
时间窗: 1 Year Post-Stem Cell Transplant
The 1-year GVHD- free relapse-free survival after HSCT (hematopoietic stem cell transplantation) conditioned with a 9Gy TMI in combination with FluBu4 and PTCY in patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), Myelodysplastic Syndrome (MDS) at high risk of relapse.
次要结局
- Overall Survival(2 Years Post-Stem Cell Transplant)
- Time To Engraftment(30 Days Post-Stem Cell Transplant)
- Adverse Events(1 Year Post-Stem Cell Transplant)
- Incidence of Acute Graft Versus Host Disease(1 Year Post-Stem Cell Transplant)
- Incidence of Chronic Graft Versus Host Disease(1 Year Post-Stem Cell Transplant)
- Transplant-Related Mortality(1 Year Post-Stem Cell Transplant)
- Adverse Events(30 Days Post-Stem Cell Transplant)
- Adverse Events(60 Days Post-Stem Cell Transplant)
- Adverse Events(90 Days Post-Stem Cell Transplant)
- Adverse Events(180 Days Post-Stem Cell Transplant)
- Incidence of Acute Graft Versus Host Disease(30 Days Post-Stem Cell Transplant)
- Incidence of Acute Graft Versus Host Disease(60 Days Post-Stem Cell Transplant)
- Incidence of Acute Graft Versus Host Disease(90 Days Post-Stem Cell Transplant)
- Incidence of Acute Graft Versus Host Disease(180 Days Post-Stem Cell Transplant)
- Incidence of Chronic Graft Versus Host Disease(180 Days Post-Stem Cell Transplant)
- Transplant-Related Mortality(30 Days Post-Stem Cell Transplant)
- Transplant-Related Mortality(60 Days Post-Stem Cell Transplant)
- Transplant-Related Mortality(90 Days Post-Stem Cell Transplant)
- Transplant-Related Mortality(180 Days Post-Stem Cell Transplant)
研究者
Matias Sanchez
Principal Investigator
University of Illinois at Chicago