A Phase Ib/2 Trial of Fludarabine/Melphalan/Total Body Irradiation With Post Transplant Cyclophosphamide as Graft Versus Host Disease Prophylaxis in Matched-Related and Matched-Unrelated Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Extensive chronic graft versus host disease (GVHD)
研究概览
简要总结
This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.
详细描述
PRIMARY OBJECTIVES:
I. To determine the cumulative incidence of extensive chronic graft versus host disease (GVHD) at 1 year after transplantation utilizing the novel conditioning/GVHD prophylactic regimen for patients undergoing allogeneic hematopoietic cell transplantation, in patients who do not progress before day 100.
SECONDARY OBJECTIVES:
I. To evaluate clinical response, engraftment rate, progression-free survival (PFS) at one year and, overall survival (OS).
II. To determine the cumulative incidence of relapse. III. To evaluate the day 100 transplant-related mortality rate. IV. To determine the cumulative incidence of grade III-IV acute GVHD.
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
- •The patient must have a diagnosis of one of the following (one must be yes):
- •Acute myeloid leukemia (AML)
- •Acute lymphoblastic leukemia (ALL)
- •Chronic lymphoblastic leukemia (CLL)
- •Chronic myelogenous leukemia (CML) (chronic phase intolerant or unresponsive to tyrosine kinase inhibitors, accelerated phase, history of blast crisis)
- •Myelodysplastic syndrome (MDS)
- •Non-Hodgkin lymphoma (NHL)
- •Hodgkin lymphoma (HL) (received and failed frontline therapy or failed autologous transplantation or inability to collect enough peripheral blood stem cells [PBSC] for autologous hematopoietic cell transplant [auto-HCT])
- •Multiple myeloma (MM)
- •Severe aplastic anemia
- •Histocompatible donor identified:
- •Related donor matched 5/6 or better (A, B, DRB1)
- •Unrelated donor matched 7/8 or better (A, B, C and DRB1)
- •Patients with severe aplastic anemia do not have disease requirements; however, if the patient has a mismatched donor, the patient must have had prior therapy with ATG.
- •The following are eligible for study inclusion:
- •Patients with MDS/MPN only require <5% myeloblast on bone marrow evaluation.
- •Patients with AML, ALL or CLL may be in CRi, patients with MM may be in VGPR
- •Patients with NHL/HL must be in CR
- •Have a Karnofsky performance status score of > 50%
- •Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation
- •Left ventricular ejection fraction > 40%
- •Bilirubin =< 3 x upper limit of normal
- •Liver alkaline phosphatase =< 3 x upper limit of normal
- •Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
- •Calculated creatinine clearance > 40 cc/min by the modified Cockroft-Gault formula
- •Patient must be cleared pre-transplant by Radiation Oncology to be able to receive 400 cGy
- •Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •Patients who have failed a prior autologous or allogeneic transplant are eligible; however, at least 6 months must have elapsed between the start of this reduced intensity conditioning regimen and the last transplant if patient had a prior autologous or myeloablative allogeneic bone marrow transplant (BMT)
- •At least 2 weeks since prior radiation treatment and/or surgery. Appropriate washout of prior chemotherapy per BMT standard of care. If medication is not on the list, go by physician discretion
- •Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Moderate to severe myelofibrosis within 60 days prior to transplant
- •Presence of human leukocyte antigen (HLA) antibodies to the donor within 60 days prior to transplant
- •Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening. (i.e., serious, uncontrolled psychiatric illness/social situations that would limit compliance with study requirements)
- •Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
- •Known human immunodeficiency virus (HIV) positive
- •Pregnant or nursing female participants
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention
研究组 & 干预措施
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Laboratory Biomarker Analysis (Other)
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Total-Body Irradiation (Radiation)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Laboratory Biomarker Analysis (Other)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Total-Body Irradiation (Radiation)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Laboratory Biomarker Analysis (Other)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Total-Body Irradiation (Radiation)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Laboratory Biomarker Analysis (Other)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Total-Body Irradiation (Radiation)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Laboratory Biomarker Analysis (Other)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Total-Body Irradiation (Radiation)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Sirolimus (Drug)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Melphalan Hydrochloride (Drug)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Mycophenolate Mofetil (Drug)
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Fludarabine Phosphate (Drug)
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Melphalan Hydrochloride (Drug)
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Mycophenolate Mofetil (Drug)
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Cyclophosphamide (Drug)
<=50 years of age Cohort A
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.
STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Sirolimus (Drug)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Cyclophosphamide (Drug)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Mycophenolate Mofetil (Drug)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Fludarabine Phosphate (Drug)
<=50 years of age Cohort B
Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Melphalan Hydrochloride (Drug)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Fludarabine Phosphate (Drug)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Cyclophosphamide (Drug)
>50 years of age Cohort A -25 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Sirolimus (Drug)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Cyclophosphamide (Drug)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Fludarabine Phosphate (Drug)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Melphalan Hydrochloride (Drug)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Mycophenolate Mofetil (Drug)
>50 years of age Cohort B 50 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Sirolimus (Drug)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Cyclophosphamide (Drug)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Fludarabine Phosphate (Drug)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Melphalan Hydrochloride (Drug)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Sirolimus (Drug)
>50 years of age Cohort C .75 mg/m2 Melphalan
Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.
干预措施: Mycophenolate Mofetil (Drug)
结局指标
主要结局
Extensive chronic graft versus host disease (GVHD)
时间窗: Up to 365 days
Will be analyzed for each stratum. Will examine in a post-hoc analysis potential chronic GVHD rates of response by human leukocyte antigen (HLA) matching status.
Extensive Chronic Graft Versus Host Disease (GVHD)
时间窗: Up to 365 days
Percentage of chronic GVHD of response by human leukocyte antigen (HLA) matching by cohort
次要结局
- Clinical response assessed as per bone marrow transplant (BMT) standard of care(Up to 4 years)
- Cumulative incidence of grade III-IV acute graft versus host disease (GVHD)(Up to 4 years)
- Cumulative incidence of relapse(Up to 4 years)
- Engraftment rate assessed as per bone marrow transplant (BMT) standard of care(Up to 4 years)
- Overall survival assessed as per bone marrow transplant (BMT) standard of care(Up to 4 years)
- Treatment-related mortality rates(Up to 4 years)
- Progression free survival (PFS) assessed as per bone marrow transplant (BMT) standard of care(At 1 year)
- Clinical Response Assessed as Per Bone Marrow Transplant (BMT) Standard of Care(Up to 4 years)
- Cumulative Incidence of Grade III-IV Acute Graft Versus Host Disease (GVHD)(Up to 4 years)
- Cumulative Incidence of Relapse(Up to 4 years)
- Engraftment Rate Assessed as Per Bone Marrow Transplant (BMT) Standard of Care(Up to 4 years)
- Overall Survival Assessed as Per Bone Marrow Transplant (BMT) Standard of Care(Up to 4 years)
- 1-Year Progression Free Survival (PFS) Rate Assessed as Per Bone Marrow Transplant (BMT) Standard of Care(At 1 year)
- Treatment-related Mortality Rates(All-Cause Mortality monitored/assessed up to 4 years. Adverse Events monitored/assessed from the start date of the conditioning regimen (Day -5) until 30 days after stem cell infusion will be reported, up to 12 months.)