Cord Blood Transplantation in Children and Young Adults With Hematologic Malignancies and Non-malignant Disorders
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Treatment related mortality at 1 year after myeloablative cord transplant
研究概览
简要总结
This is a single-arm study to investigate 1-year treatment related mortality (TRM) in patients with life threatening non-malignant and malignant hematologic disorders who do not have a matched related donor for allogeneic transplantation.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant Inclusion Criteria:
- •Age and Donor Status:
- •Patients with age ≤ 21 years at time of consent with no available and suitably matched related or unrelated donor in the required time period.
- •Diagnoses :
- •I. Acute myelogenous leukemia (AML) :
- •Complete first remission (CR1) at high risk for relapse such as any of the following:
- •Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder (MPS).
- •Therapy-related AML (t-AML).
- •White cell count at presentation > 100,
- •Presence of extramedullary leukemia at diagnosis.
- •Any unfavorable subtype by FAB or WHO classification.
- •High-risk cytogenetics (e.g. those associated with MDS, abnormalities of 5, 7, 8, complex karyotype) or high-risk molecular abnormalities.
- •Requirement for 2 or more inductions to achieve CR
- •Presence of Minimal Residual Disease (MRD+) by cytogenetics, flow cytometry or molecular methods after induction.
- •Any patient with newly diagnosed AML with intermediate risk cytogenetics who elects allograft with curative intent over consolidation chemotherapy.
- •Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician.
- •Other high-risk features not defined above.
- •Complete second remission (CR2).
- •Primary refractory or relapsed AML with less than 10% blasts by bone marrow morphology. Patients with cytogenetic, flow cytometric, or molecular abnormalities in ≤ 10% of cells are eligible.
- •II. Acute lymphoblastic leukemia (ALL):
- •Complete first remission (CR1) at high risk for relapse such as any of the following:
- •White cell count at presentation > 30,000 for B-cell lineage and > 100,000 for T-cell lineage.
- •Presence of any high-risk cytogenetic abnormalities such as t (9;22), t (1;19), t (4;11) or other MLL rearrangements (11q23) or other high-risk molecular abnormality.
- •Failure to achieve complete remission (CR) after four weeks of induction therapy.
- •Persistence or recurrence of MRD on therapy.
- •Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.
- •Other high-risk features not defined above.
- •Complete second remission (CR2).
- •Primary refractory or relapsed ALL with MRD disease after antibody therapy (e.g., blinatumomab, inotuzumab, other) and/or CAR-T cell therapy.
- •III. Other acute leukemias:
- •Leukemias of ambiguous lineage or of other types (e.g. blastic plasmacytoid dendritic cell neoplasm) with less than 5% blasts by BM morphology. Patients with persistent/relapsed disease with cytogenetic, flow cytometric or molecular aberrations in ≤ 5% of cells are eligible.
- •IV. Myelodysplastic Syndrome (MDS) / Myeloproliferative Disorders (MPD) other than myelofibrosis:
- •International prognostic scoring system (IPSS) risk score of INT-2 or high risk at the time of diagnosis.
- •Any IPSS risk category if life-threatening cytopenia(s) exists.
- •Any IPSS risk category with karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia.
- •MDS/ myeloproliferative disorder overlap syndromes without myelofibrosis.
- •MDS/ MPD patients must have less than 10% bone marrow myeloblasts and ANC ≥ 0.2 (growth factor supported if necessary) at transplant work-up.
- •V. Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) at high-risk of relapse or progression if not in remission:
- •Eligible patients with aggressive histology (such as, but not limited to, diffuse large B-cell NHL, mantle cell NHL, and T-cell histology) in CR.
- •Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) will have 2nd or subsequent progression with stable disease/ CR/ PR with no single lesion equal to or more than 5 cm.
- •Eligible patients with HL will be those without progression of disease (POD) after salvage chemotherapy with no single lesion ≥ 5 cm.
- •VI. Inherited Metabolic Disorders [also see EBMT Handbook for discussion on patient eligibility for allogeneic transplant; in general, patients are considered early in the disease course, before they develop neurologic symptoms (46)]:
- •Hurler Syndrome
- •Hunter (MPS 2 - early disease)
- •Sly syndrome (MPSVIII)
- •α-Mannosidosis
- •Osteopetrosis
- •Metachromatic Leukodystrophy
- •Globoid (GLD)
- •VII. Non-Malignant disorders (other) [also see EBMT Handbook for criteria for transplant (46)]
- 另有 21 项未显示
排除标准
- •Inadequate performance status/ organ function.
- •Advanced metabolic disease (EBMT handbook).
- •Active CNS leukemic involvement.
- •Indolent NHL or Hodgkin lymphoma with progression of disease after most recent salvage chemotherapy.
- •Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis.
- •Autologous stem cell transplant within the preceding 6 months.
- •Any prior allogeneic stem cell transplant.
- •Active and uncontrolled infection (bacterial/fungal/viral) at time of transplantation.
- •HIV infection.
- •Seropositivity for HTLV-
- •Pregnancy or breast feeding.
- •Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, long-term follow-up, and research tests.
研究组 & 干预措施
Participants with malignant hematologic disorders
Patients with malignant disorders receive clofarabine intravenously (IV) over 2 hours, fludarabine phosphate (fludarabine) IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or orally (PO) and mycophenolate mofetil IV over at least 2 hours in the absence of unacceptable toxicity. Patients may begin to taper tacrolimus at approximately 3 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing graft versus host disease (GVHD) requiring systemic immune suppression. TRANSPLANT: Patients undergo cord blood transplantation (CBT) on day 0.**Subgroup will get rATG (day -12 to -10) POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim subcutaneously (SC) or IV over 15-30 minutes until absolute neutrophil count (ANC) recovery. Additionally, patients undergo blood sample collection, computed tomography (CT) and positron emission tomography (PET) on study.
干预措施: Clofarabine (Drug)
Participants with malignant hematologic disorders
Patients with malignant disorders receive clofarabine intravenously (IV) over 2 hours, fludarabine phosphate (fludarabine) IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or orally (PO) and mycophenolate mofetil IV over at least 2 hours in the absence of unacceptable toxicity. Patients may begin to taper tacrolimus at approximately 3 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing graft versus host disease (GVHD) requiring systemic immune suppression. TRANSPLANT: Patients undergo cord blood transplantation (CBT) on day 0.**Subgroup will get rATG (day -12 to -10) POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim subcutaneously (SC) or IV over 15-30 minutes until absolute neutrophil count (ANC) recovery. Additionally, patients undergo blood sample collection, computed tomography (CT) and positron emission tomography (PET) on study.
干预措施: Fludarabine (Drug)
Participants with malignant hematologic disorders
Patients with malignant disorders receive clofarabine intravenously (IV) over 2 hours, fludarabine phosphate (fludarabine) IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or orally (PO) and mycophenolate mofetil IV over at least 2 hours in the absence of unacceptable toxicity. Patients may begin to taper tacrolimus at approximately 3 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing graft versus host disease (GVHD) requiring systemic immune suppression. TRANSPLANT: Patients undergo cord blood transplantation (CBT) on day 0.**Subgroup will get rATG (day -12 to -10) POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim subcutaneously (SC) or IV over 15-30 minutes until absolute neutrophil count (ANC) recovery. Additionally, patients undergo blood sample collection, computed tomography (CT) and positron emission tomography (PET) on study.
干预措施: Busulfan (Drug)
Participants with malignant hematologic disorders
Patients with malignant disorders receive clofarabine intravenously (IV) over 2 hours, fludarabine phosphate (fludarabine) IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or orally (PO) and mycophenolate mofetil IV over at least 2 hours in the absence of unacceptable toxicity. Patients may begin to taper tacrolimus at approximately 3 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing graft versus host disease (GVHD) requiring systemic immune suppression. TRANSPLANT: Patients undergo cord blood transplantation (CBT) on day 0.**Subgroup will get rATG (day -12 to -10) POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim subcutaneously (SC) or IV over 15-30 minutes until absolute neutrophil count (ANC) recovery. Additionally, patients undergo blood sample collection, computed tomography (CT) and positron emission tomography (PET) on study.
干预措施: Cyclosporine-A (Drug)
Participants with malignant hematologic disorders
Patients with malignant disorders receive clofarabine intravenously (IV) over 2 hours, fludarabine phosphate (fludarabine) IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or orally (PO) and mycophenolate mofetil IV over at least 2 hours in the absence of unacceptable toxicity. Patients may begin to taper tacrolimus at approximately 3 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing graft versus host disease (GVHD) requiring systemic immune suppression. TRANSPLANT: Patients undergo cord blood transplantation (CBT) on day 0.**Subgroup will get rATG (day -12 to -10) POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim subcutaneously (SC) or IV over 15-30 minutes until absolute neutrophil count (ANC) recovery. Additionally, patients undergo blood sample collection, computed tomography (CT) and positron emission tomography (PET) on study.
干预措施: Mycophenolate Mofetil (Drug)
Participants with malignant hematologic disorders
Patients with malignant disorders receive clofarabine intravenously (IV) over 2 hours, fludarabine phosphate (fludarabine) IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or orally (PO) and mycophenolate mofetil IV over at least 2 hours in the absence of unacceptable toxicity. Patients may begin to taper tacrolimus at approximately 3 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing graft versus host disease (GVHD) requiring systemic immune suppression. TRANSPLANT: Patients undergo cord blood transplantation (CBT) on day 0.**Subgroup will get rATG (day -12 to -10) POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim subcutaneously (SC) or IV over 15-30 minutes until absolute neutrophil count (ANC) recovery. Additionally, patients undergo blood sample collection, computed tomography (CT) and positron emission tomography (PET) on study.
干预措施: Cord Blood Graft (Biological)
Participants with non-malignant hematologic disorders
Patients with non-malignant disorders receive rituximab IV on day -12 and rabbit anti-thymocyte globulin (rATG) over 12 hours on day -12 to -9. Patients then receive clofarabine IV over 2 hours, fludarabine IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or PO and mycophenolate mofetil IV over at least 2 hours. Patients may begin to taper tacrolimus at approximately 6 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing GVHD requiring systemic immune suppression.
TRANSPLANT: Patients undergo CBT on day 0. POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim SC or IV over 15-30 minutes until ANC recovery. Patients also receive rituximab IV on day 30.
Additionally, patients undergo blood sample collection, CT and PET on study.
干预措施: Clofarabine (Drug)
Participants with non-malignant hematologic disorders
Patients with non-malignant disorders receive rituximab IV on day -12 and rabbit anti-thymocyte globulin (rATG) over 12 hours on day -12 to -9. Patients then receive clofarabine IV over 2 hours, fludarabine IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or PO and mycophenolate mofetil IV over at least 2 hours. Patients may begin to taper tacrolimus at approximately 6 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing GVHD requiring systemic immune suppression.
TRANSPLANT: Patients undergo CBT on day 0. POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim SC or IV over 15-30 minutes until ANC recovery. Patients also receive rituximab IV on day 30.
Additionally, patients undergo blood sample collection, CT and PET on study.
干预措施: Fludarabine (Drug)
Participants with non-malignant hematologic disorders
Patients with non-malignant disorders receive rituximab IV on day -12 and rabbit anti-thymocyte globulin (rATG) over 12 hours on day -12 to -9. Patients then receive clofarabine IV over 2 hours, fludarabine IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or PO and mycophenolate mofetil IV over at least 2 hours. Patients may begin to taper tacrolimus at approximately 6 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing GVHD requiring systemic immune suppression.
TRANSPLANT: Patients undergo CBT on day 0. POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim SC or IV over 15-30 minutes until ANC recovery. Patients also receive rituximab IV on day 30.
Additionally, patients undergo blood sample collection, CT and PET on study.
干预措施: Busulfan (Drug)
Participants with non-malignant hematologic disorders
Patients with non-malignant disorders receive rituximab IV on day -12 and rabbit anti-thymocyte globulin (rATG) over 12 hours on day -12 to -9. Patients then receive clofarabine IV over 2 hours, fludarabine IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or PO and mycophenolate mofetil IV over at least 2 hours. Patients may begin to taper tacrolimus at approximately 6 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing GVHD requiring systemic immune suppression.
TRANSPLANT: Patients undergo CBT on day 0. POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim SC or IV over 15-30 minutes until ANC recovery. Patients also receive rituximab IV on day 30.
Additionally, patients undergo blood sample collection, CT and PET on study.
干预措施: Cyclosporine-A (Drug)
Participants with non-malignant hematologic disorders
Patients with non-malignant disorders receive rituximab IV on day -12 and rabbit anti-thymocyte globulin (rATG) over 12 hours on day -12 to -9. Patients then receive clofarabine IV over 2 hours, fludarabine IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or PO and mycophenolate mofetil IV over at least 2 hours. Patients may begin to taper tacrolimus at approximately 6 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing GVHD requiring systemic immune suppression.
TRANSPLANT: Patients undergo CBT on day 0. POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim SC or IV over 15-30 minutes until ANC recovery. Patients also receive rituximab IV on day 30.
Additionally, patients undergo blood sample collection, CT and PET on study.
干预措施: Mycophenolate Mofetil (Drug)
Participants with non-malignant hematologic disorders
Patients with non-malignant disorders receive rituximab IV on day -12 and rabbit anti-thymocyte globulin (rATG) over 12 hours on day -12 to -9. Patients then receive clofarabine IV over 2 hours, fludarabine IV over 30 minutes, and busulfan IV over 3 hours on days -5 to -2. Beginning on day -3, patients receive tacrolimus IV or PO and mycophenolate mofetil IV over at least 2 hours. Patients may begin to taper tacrolimus at approximately 6 months post-transplant and mycophenolate mofetil at approximately 60 days post-transplant in the absence of ongoing GVHD requiring systemic immune suppression.
TRANSPLANT: Patients undergo CBT on day 0. POST-TRANSPLANT: Beginning on day 7, patients receive filgrastim SC or IV over 15-30 minutes until ANC recovery. Patients also receive rituximab IV on day 30.
Additionally, patients undergo blood sample collection, CT and PET on study.
干预措施: Cord Blood Graft (Biological)
结局指标
主要结局
Treatment related mortality at 1 year after myeloablative cord transplant
时间窗: 1 year
The primary objective of this study is to assess treatment related mortality (TRM) at 1 year after myeloablative cord transplant.
次要结局
未报告次要终点