MT2023-20: Hematopoietic Cell Transplant With Reduced Intensity Conditioning and Post-transplant Cyclophosphamide for Severe Aplastic Anemia and Other Forms of Acquired Bone Marrow Failure.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Incidence of chronic GvHD-free, failure-free survival (GFFS)
研究概览
简要总结
A phase II trial of a reduced intensity conditioned (RIC) allogeneic hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) for idiopathic severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria (PNH), acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT) utilizing population pharmacokinetic (popPK)-guided individual dosing of pre-transplant conditioning and differential dosing of low dose total body irradiation based on age, presence of myelodysplasia and/or clonal hematopoiesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic Severe Aplastic Anemia (SAA), characterized by one of the following:
- •Refractory cytopenia(s), with 1+ of the following:
- •Platelets <20,000/uL or transfusion dependent
- •Absolute neutrophil count <500/uL without hematopoietic growth factor support
- •Absolute reticulocyte count <60,000/uL AND bone marrow cellularity <50% (with < 30% residual hematopoietic cells)
- •Early myelodysplastic features (bone marrow (BM) blasts <5%), without history of MDS/AML pre-treatment.
- •Idiopathic SAA with post-HCT graft failure (blood/marrow donor chimerism <5%) requiring a 2nd allogeneic HCT
- •Paroxysmal Nocturnal Hemoglobinuria (PNH), including AA-PNH overlap syndrome, acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT), characterized by one of the following:
- •Refractory cytopenia(s), with 1+ of the following:
- •Platelets <20,000/uL or transfusion dependent
- •Absolute neutrophil count <500/uL without hematopoietic growth factor support
- •Absolute reticulocyte count <60,000/uL or red cell transfusion dependent AND Bone marrow evidence of 1 to 3-lineage aplasia OR peripheral blood PNH clone >/= 10%
- •Early myelodysplastic features (bone marrow (BM) blasts <5%) without history of MDS/AML pre-treatment.
- •Idiopathic PNH, aPRCA, or aAT with post-HCT graft failure (blood/marrow donor chimerism <5%) requiring a 2nd allogeneic HCT
- •Adequate organ function within 30 days of conditioning regimen
排除标准
- •Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment
- •Uncontrolled infection
- •Evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
- •Known allergy to any of the study components
- •Prior radiation therapy deemed excessive by radiation therapist for proposed low dose TBI exposure on this protocol
- •Diagnosis of an inherited bone marrow failure disorder such as Fanconi anemia, Telomere biology disorder, or Schwachman-Diamond syndrome, unless reviewed by the principal investigator and deemed appropriate for this approach (e.g. GATA2 deficiency)
- •Advanced myelodysplastic syndrome (MDS; BM blasts >5%) or acute myeloid leukemia
- •Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements
- •Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study
研究组 & 干预措施
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Cell Infusion (Biological)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Post-Transplant G-CSF (Drug)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Total Body Irradiation (Radiation)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Total Body Irradiation (Radiation)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Cell Infusion (Biological)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Post-Transplant G-CSF (Drug)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Cyclophosphamide (Drug)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Mycophenolate Mofetil (Drug)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Fludarabine (Drug)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Rabbit ATG (Drug)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Rituximab (Drug)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Fludarabine (Drug)
Arm A: No clonal hematopoiesis
Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Tacrolimus (Drug)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Rabbit ATG (Drug)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Rituximab (Drug)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Cyclophosphamide (Drug)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Tacrolimus (Drug)
Arm B: Clonal hematopoiesis
Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.
干预措施: Mycophenolate Mofetil (Drug)
结局指标
主要结局
Incidence of chronic GvHD-free, failure-free survival (GFFS)
时间窗: 1 year post HCT
Incidence of chronic GvHD-free, failure-free survival (GFFS) 1 year post HCT
Incidence of chronic GvHD-free survival
时间窗: 1 year post HCT
Incidence of chronic GvHD-free survival at 1 year post HCT
Incidence of grade 3-4 acute GvHD
时间窗: 1 year post HCT
Incidence of grade 3-4 acute graft-versus host disease (GvHD) at 1 year post HCT.
次要结局
- Incidence of neutrophil recovery(Day 42 post HCT)
- Incidence of platelet recovery(6 months post HCT)
- Incidence of grade 3-4 acute GvHD(100 days post HCT)
- Overall survival(1 and 2 years post HCT)
- Incidence of chronic GvHD-free survival(2 years post HCT)
- Incidence of failure-free survival (GFFS)(2 years post HCT)
- Incidence of any chronic GvHD(1 year post HCT)