A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 9
- 主要终点
- Neutrophil Engraftment
研究概览
简要总结
The goal of this clinical trial is to determine the safety and feasibility of allogeneic transplantation with bone marrow from a deceased donor in patients with acute and chronic leukemias, myelodysplastic syndrome, and certain lymphomas. Patients will either receive myeloablative conditioning or reduced intensity conditioning regimen prior to the transplant. Patients will be followed for 56 days for safety endpoints and remain in follow-up for one year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has the ability to provide informed consent according to the applicable regulatory and local institutional requirements
- •Male or female, aged ≥18 and ≤65 years for patients receiving MAC (Regimen A or Regimen B); aged ≥18 and ≤75 years for patients receiving RIC (Regimen C or D)
- •Patient must require allogeneic HCT per the discretion of the treating physician
- •Patient must be high-resolution, HLA partially or fully matched (4-8/8 allele matched at HLA-A, -B, -C, DRB1) to an available Ossium HPC, Marrow product
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Diagnosed with malignant hematologic disease including:
- •Acute leukemia [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute biophenotypic leukemia (ABL), or acute undifferentiated leukemia (AUL)], MDS without fibrosis, or chronic leukemia (CLL, CML) in the first remission or beyond with ≤5% marrow blasts documented by bone marrow assessment and no circulating blasts or extra-medullary disease within 42 days prior to anticipated start of conditioning
- •Chemosensitive non-Hodgkin's lymphomas, Hodgkin's lymphoma, or cutaneous T cell lymphomas in the first remission or beyond documented by PET/CT imaging and bone marrow assessment within 42 days prior to anticipated start of conditioning
- •Karnofsky performance status score ≥70% (MAC) or ≥60% (RIC)
- •HCT comorbidity index (HCT-CI) ≤5
- •Adequate organ function defined as:
- •Cardiac: LVEF at rest ≥40% (RIC) or LVEF at rest ≥45% (MAC)
- •Pulmonary: DLCO, FEV1, FVC ≥50% predicted by pulmonary function tests (PFTs). DLCO value may be corrected for hemoglobin.
- •Hepatic: total bilirubin ≤2.0 mg/dL, and ALT, AST, and ALP <3 x upper limit normal (ULN), unless ALT, AST, and/or ALP are disease related
- •Renal: SCr within 1.5x normal range for age. If SCr is outside normal range for age, CrCl> 60 mL/min/1.73m2 must be obtained (measured by 24-hour urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR)
排除标准
- •Availability of suitable graft from living donor (defined as 7/8 or 8/8 HLA-matched related or unrelated donors, haploidentical donors, or cord blood donors)
- •Prior autologous or allogeneic HCT
- •Pregnancy or lactation
- •Ongoing treatment with an investigational drug used for disease-related treatment within 5 half-lives of the drug
- •Current uncontrolled bacterial, viral or fungal infection defined as currently taking medication with evidence of progression of clinical symptoms or radiologic findings
- •Any condition(s) or diagnosis, both physical or psychological, or physical exam finding that in the investigator's opinion precludes participation
研究组 & 干预措施
Cohort 1
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant myeloablative conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D (RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Ossium HPC Marrow, Bone Marrow Transplant (Other)
Cohort 1
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant myeloablative conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D (RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Pre-transplant conditioning - Myeloablative (MAC) (Other)
Cohort 1
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant myeloablative conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D (RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Pre-transplant conditioning - Reduced Intensity (RIC) (Other)
Cohort 1
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant myeloablative conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D (RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Post-transplant treatment (Other)
Cohort 2
*Open to enrollment after DSMB review of Cohort 1 safety events through Day 56*
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D(RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Ossium HPC Marrow, Bone Marrow Transplant (Other)
Cohort 2
*Open to enrollment after DSMB review of Cohort 1 safety events through Day 56*
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D(RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Pre-transplant conditioning - Myeloablative (MAC) (Other)
Cohort 2
*Open to enrollment after DSMB review of Cohort 1 safety events through Day 56*
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D(RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Pre-transplant conditioning - Reduced Intensity (RIC) (Other)
Cohort 2
*Open to enrollment after DSMB review of Cohort 1 safety events through Day 56*
Bone Marrow Transplant with Ossium HPC, Marrow
Pre-transplant conditioning treatment with:
Regimen A(MAC): Busulfan and Fludarabine
[OR]
Regimen B(MAC): Fludarabine and Total Body Irradiation
[OR]
Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation
[OR]
Regimen D(RIC): Fludarabine, Melphalan, and Total Body Irradiation
Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim
干预措施: Post-transplant treatment (Other)
结局指标
主要结局
Neutrophil Engraftment
时间窗: Day 28
Neutrophil engraftment is defined as achieving an absolute neutrophil count (ANC) of greater than or equal to 500/µL for 3 consecutive measurements on 3 different days by Day 28.
Serious Adverse Events
时间窗: Day 56
Occurrence of any event classified as SAE. The time of occurrence of each serious adverse event will be recorded.
CTCAE Grade 3/4 Adverse Events (AEs)
时间窗: Day 56
Occurrence of any event classified as grade 3/4 AE attributed to Ossium HPC, Marrow per the CTCAE v5.0 guidelines. The time of the occurrence of each event will be recorded.
CTCAE Grade 3/4 Adverse Events (AEs) attributed to infusion of Ossium HPC, Marrow
时间窗: Day 28
Occurrence of any event classified as grade 3 or higher attributed to Ossium HPC, Marrow infusion per the CTCAE v5.0 guidelines. The time of the occurrence will be recorded.
Death
时间窗: Day 56
The time of death will be recorded for each expired patient.
次要结局
- Cumulative incidences of neutrophil engraftment(Day 28)
- Incidence of clinically-significant infections(Day 100 and Day 365)
- Cumulative incidences of platelet recovery(Day 56)
- Cumulative incidence of disease relapses(Day 365)
- Transplant-related mortality (TRM)(Day 100 and Day 365)
- Cumulative incidences of acute (aGVHD) Graft Versus Host Disease(Day 100, Day 180, and Day 365)
- Cumulative incidences of chronic (cGVHD) Graft Versus Host Disease(Day 100, Day 180, and Day 365)