Pilot Study: Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Progenitor Cells (Dilanubicel) in the Setting of Single Cord Blood Transplantation for Patients With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Incidence of graft failure
研究概览
简要总结
This phase II trial studies how well donor umbilical cord blood transplant with ex-vivo expanded cord blood progenitor cells (dilanubicel) works in treating patients with blood cancer. Before the transplant, patients will receive chemotherapy (fludarabine, cyclophosphamide and in some cases thiotepa) and radiation therapy. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.
详细描述
OUTLINE:
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine intravenously (IV) over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total body irradiation (TBI) twice daily (BID) on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI once daily (QD) on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo multigated acquisition scan (MUGA) or echocardiography (ECHO), and computed tomography (CT) during screening. Patients also undergo blood sample collection on study.
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
- 10 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 10 to 65 years old with a hematologic malignancy in need of hematopoietic cell transplant who are > 30 kg and without a suitable related donor
- •Patient must have hematologic malignancy that meets institutional eligibility requirements for cord blood transplant
- •Malignancies included are:
- •Acute leukemia, including acute myeloid leukemia (AML), biphenotypic acute leukemia or mixed-lineage leukemia, acute lymphoblastic leukemia (ALL); all patients must be in complete response (CR) as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with adequate cellularity to assess remission status
- •Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% in a representative bone marrow aspirate
- •Chronic myeloid leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy
- •High dose TBI regimen: 10 to =< 45 years
- •Intermediate intensity regimen: 10 to =< 65 years
- •Patients 10 to =< 45 years: Lansky (< 16 years old) or Karnofsky (>= 16 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1
- •Patients > 45 to =< 65 years: Karnofsky >= 70 or ECOG 0-1 and non-age adjusted comorbidity index =< 5
- •Adults: Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL
- •Children (< 18 years old): Calculated creatinine clearance must be > 60 mL/min
- •Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
- •Transaminases must be < 3 x the upper limit of normal per reference values of treating institution
- •Carbon monoxide diffusing capability (DLCO) corrected >= 60% normal (may not be on supplemental oxygen)
- •For pediatric patients unable to perform pulmonary function tests, O2 saturation > 92% on room air
- •Left ventricular ejection fraction >= 50% OR
- •Shortening fraction > 26%
- •Ability of participant or legally authorized representative to understand and the willingness to sign a written informed consent form
- •DONOR: Minimum requirement: The cord blood (CB) unit must be matched at a minimum at 4/6 HLA-A, B antigens and DRB1 allele with the recipient; therefore, 0-2 mismatches at the A or B or DRB1 loci based on intermediate resolution at HLA-A, B and high resolution allele level typing at HLA- DRB1 are allowed
- •DONOR: Institutional guidelines for HLA-match may be followed as long as the minimum criteria for HLA-matching as above are met
- •DONOR: The CB unit selected for transplant must have a MINIMUM of 2.5 x 10^7 TNC/kg
- •DONOR: The minimum recommended CD34/kg cell dose is 1.7 x 10^5 CD34/kg
- •DONOR: A backup unit must be identified and reserved prior to the start of the treatment plan for possible infusion in the unlikely event of poor post-thaw viability of the primary CB unit. A suitable back up unit will be considered, as follows:
- •Must be matched at a minimum at 4/6 HLA-A, B, DRBl loci with the recipient. Therefore 0-2 mismatches at the A or B or DRBl loci based on intermediate resolution A, B antigen and DRBl allele typing for determination of HLA-match is allowed (Fred Hutch Protocol 2010).
- •Must contain a MINIMUM of 1.5 x 10^7 TNC/kg to ensure the same requirement we use for a standard double CBT per CB selection guideline (Fred Hutch Protocol 2010).
排除标准
- •Uncontrolled viral or bacterial infection at the time of study enrollment
- •Active or recent (prior 6 month) invasive fungal infection unless cleared by infectious disease (ID) consult
- •History of human immunodeficiency virus (HIV) infection
- •Pregnant or breastfeeding
- •Prior allogeneic transplant
- •Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy; diagnostic lumbar puncture is to be performed
研究组 & 干预措施
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Dilanubicel (Biological)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Thiotepa (Drug)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Umbilical Cord Blood Transplantation (Procedure)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Bone Marrow Biopsy (Procedure)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Total-Body Irradiation (Radiation)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Biospecimen Collection (Procedure)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Bone Marrow Aspirate (Procedure)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Multigated Acquisition Scan (Procedure)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Electrocardiography (Procedure)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Computed Tomography (Procedure)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Cyclophosphamide (Drug)
Treatment (chemotherapy, TBI, NLA101)
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.
All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Incidence of graft failure
时间窗: Up to day 45 post-transplant
Primary graft failure/rejection as defined by no neutrophil recovery (regardless of donor chimerism) or autologous recovery (neutrophil recovery but \< 10% donor chimerism in blood and bone marrow \[BM\]).
次要结局
- Time to neutrophil engraftment(Up to day 45 post-transplant)
- Time to platelet engraftment(Up to day 100 post-transplant)
- Incidence of adverse events(Up to day 100 post-transplant)
- Incidence of non-relapse mortality(At 1 year post-transplant)
- Incidence and severity of acute graft versus host disease (GVHD)(At day 100 post-transplant)
- Incidence and severity of chronic graft versus host disease (GVHD)(Up to approximately 2 years post-transplant)
研究者
Filippo Milano
Associate Professor
Fred Hutchinson Cancer Center