NCT02178683Unknown3 期
Tacrolimus and Mycophenolate Mofetil as Post-Grafting Immunosuppression After Conditioning With Fludarabine and Low-Dose Total Body Irradiation for Recipients of HLA-Matched or Mis-Matched Family or Unrelated Donor HCT
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Engraftment
研究概览
简要总结
This protocol will evaluate Tacrolimus and MMF after conditioning with fludarabine and low-dose TBI in patients who are not candidates for conventional allografting. A novel approach to immunosuppression will be tested incorporating an early but extended taper of Tacrolimus starting on day +80 or in the case of relapse. The goal is to induce early immunity and GVT effects without compromising GVHD control. The anti-metabolite MMF will be re-introduced on day +100 to try and induce tolerance and block chronic GVHD during the taper of the Tacrolimus. DLI may be given in the presence of disease progression but not for mixed chimerism as in previous protocols.
详细描述
OBJECTIVES
Major Objectives A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients receiving a non-myeloablative allogeneic SCT from an HLA-Identical or non-identical family donor or unrelated donors, with fludarabine and low-dose TBI, with immunosuppression utilizing tacrolimus and MMF.
B. To evaluate the incidence of grade II-IV GVHD associated with this treatment.
C. To evaluate the engraftment when donors who are not HLA-identical family members are utilized for allogeneic stem cell transplantation.
D. To evaluate the incidence of GVHD using three times per day MMF after unrelated donor stem cell transplants or two times per day MMF after family donor stem cell transplant.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with AML, ALL, CML, CLL, myelodysplastic syndrome (MDS), NHL, Hodgkin's disease (HD), paroxysmal nocturnal hemoglobinuria (PNH), hypoproliferative dysplasia with or without increased blasts, or myeloma, who are at significantly higher than usual risk for mortality from conventional myeloablative allogeneic SCT due to age or comorbidities:
- •Age ≥ to 50 years with AML or ALL in complete remission or with <18% blasts in bone marrow
- •Age ≥ to 50 years with MDS or CML.
- •Age 16 to 75 years with lymphomas or myeloma, who have failed chemotherapy and are not candidates for an autologous transplant, or who have failed a prior autologous SCT.
- •Patients of any age with CLL or low-grade NHL. Patients with CLL and low-grade NHL need to have failed at least first-line treatment, with an alkylating agent, fludarabine or 2-chlorodeoxyadenosine (2-CDA), or anti-CD20 monoclonal antibody rituximab.
- •Patients of any age with marrow failure
- •Patients ≥60 years old will first be considered for an allogeneic stem cell transplant from a family member and will be offered an unrelated donor transplant only if no suitable family member, preferably an HLA-matched sibling, is available.
- •Patients with hematological malignancy relapsed after prior auto transplantation.
- •Patients at high-risk (>60%) of relapsing after autologous transplantation for hematological malignancies may receive allogeneic transplant as "consolidative immunotherapy". Diagnoses include MM, non-HL, HL, AML, ALL and MDS. Minimal duration between auto and allo transplants is 4 weeks.
- •Patients of any age with hematologic malignancies treatable by allo SCT, who, because of pre-existing medical conditions or the disease itself (Fanconi anemia or PNH), are considered to be at significantly increased risk for transplant toxicity using high-dose transplantation regimens.
- •Patients with metastatic renal cell carcinoma. Must have include good performance status (Karnofsky score ≥ 60%), no active brain metastases, life expectancy of at least 6 months, absence of bulky liver metastases. Patients will be treated on other active disease-specific protocols when available.
- •Patients with other malignant diseases treatable with allogeneic SCT may be eligible for this protocol on a case by case basis, if approved by the principal investigator and the BMT attending physicians group.
- •Available HLA-identical, a one-antigen mis-matched sibling donor, a phenotypically HLA-matched family member, a phenotypically matched unrelated donor, or a 9/10 matched unrelated donor.
- •Age ≤ 75 years.
排除标准
- •Patients with hematological malignancies eligible for a curative autologous SCT: intermediate- or high-grade NHL with chemo-sensitive first relapse.
- •HD with chemo-sensitive first relapse.
- •Otherwise healthy patients who are eligible for a conventional myeloablative allogeneic SCT.
- •Patients with rapidly progressive intermediate or high-grade NHL, unless in minimal disease state after the last treatment.
- •Patients with active uncontrolled CNS involvement with malignancy.
- •Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
- •Females who are pregnant.
- •Patients who are HIV positive
- •Organ dysfunction
- •Left ventricle ejection fraction < 35%.
- •DLCO <35% of predicted, or receiving continuous supplementary oxygen.
- •Liver function tests: total bilirubin >2x the upper limit of normal, and/or transaminases >4x the upper limit of normal.
- •Karnofsky score <50 for patients < 60 years, or <70 for patients aged 60 - 69 years
- •Creatinine clearance < 60 ml/min.
- •Patients with hypertension that is poorly controlled on antihypertensive therapy.
- •Patients with a positive PRA or anti-donor T or B cell (+) will be considered for this treatment protocol only if no other option is available.
研究组 & 干预措施
Tacrolimus and Mycophenolate Mofetil
No Intervention
Non-myeloablative allogeneic SCT from an HLA-Identical or non-identical family onor or unrelated donors, with fludarabine and low-dose TBI, with immunosuppression utilizing tacrolimus and MMF.
干预措施: Tacrolimus and MMF. (Drug)
结局指标
主要结局
Engraftment
时间窗: Post 100 days
To measure safe, stable engraftment using Tacrolimus and Mycophenolate Mofetil as post-grafting immunosuppression in patients following conditioning with fludarabine and total-body irradiation for allogeneic stem cell transplant.
次要结局
- Graft Versus Host Disease(Post 100 days)
研究者
Peter McSweeney, M.D.
Principal Investigator
Colorado Blood Cancer Institute
研究点 (1)
Loading locations...
相似试验
已完成
2 期
Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic CancerMyelodysplastic/Myeloproliferative Neoplasm, UnclassifiablePreviously Treated Myelodysplastic SyndromeRefractory Chronic Lymphocytic LeukemiaRefractory Plasma Cell MyelomaWaldenstrom MacroglobulinemiaAccelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveAdult Acute Lymphoblastic Leukemia in RemissionAdult Acute Myeloid Leukemia in RemissionAdult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLLAdult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARAAdult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1Atypical Chronic Myeloid Leukemia, BCR-ABL1 NegativeBlast Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveChildhood Acute Lymphoblastic Leukemia in RemissionChildhood Acute Myeloid Leukemia in RemissionChildhood Burkitt LymphomaChildhood Chronic Myelogenous Leukemia, BCR-ABL1 PositiveChildhood Diffuse Large Cell LymphomaChildhood Immunoblastic LymphomaChildhood Myelodysplastic SyndromeStage II Contiguous Adult Burkitt LymphomaStage II Contiguous Adult Diffuse Large Cell LymphomaStage II Contiguous Adult Diffuse Mixed Cell LymphomaStage II Contiguous Adult Diffuse Small Cleaved Cell LymphomaStage II Adult Contiguous Immunoblastic LymphomaStage II Contiguous Adult Lymphoblastic LymphomaStage II Grade 1 Contiguous Follicular LymphomaStage II Grade 2 Contiguous Follicular LymphomaStage II Grade 3 Contiguous Follicular LymphomaStage II Contiguous Mantle Cell LymphomaStage II Non-Contiguous Adult Burkitt LymphomaStage II Non-Contiguous Adult Diffuse Large Cell LymphomaStage II Non-Contiguous Adult Diffuse Mixed Cell LymphomaStage II Non-Contiguous Adult Diffuse Small Cleaved Cell LymphomaStage II Adult Non-Contiguous Immunoblastic LymphomaStage II Non-Contiguous Adult Lymphoblastic LymphomaStage II Grade 1 Non-Contiguous Follicular LymphomaStage II Grade 2 Non-Contiguous Follicular LymphomaStage II Grade 3 Non-Contiguous Follicular LymphomaStage II Non-Contiguous Mantle Cell LymphomaStage II Small Lymphocytic LymphomaRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Acute Myeloid LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Myeloid LeukemiaRecurrent Childhood Anaplastic Large Cell LymphomaRecurrent Childhood Large Cell LymphomaRecurrent Childhood Lymphoblastic LymphomaRecurrent Childhood Burkitt LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaRecurrent Childhood Hodgkin LymphomaRecurrent Chronic Myelogenous Leukemia, BCR-ABL1 PositiveSecondary Myelodysplastic SyndromeStage I Adult Burkitt LymphomaStage I Adult Diffuse Large Cell LymphomaStage I Adult Diffuse Mixed Cell LymphomaStage I Adult Immunoblastic LymphomaStage I Adult Lymphoblastic LymphomaStage I Childhood Anaplastic Large Cell LymphomaStage I Childhood Large Cell LymphomaStage I Childhood Lymphoblastic LymphomaStage I Childhood Burkitt LymphomaStage I Grade 1 Follicular LymphomaStage I Grade 2 Follicular LymphomaStage I Grade 3 Follicular LymphomaStage I Mantle Cell LymphomaStage I Marginal Zone LymphomaStage I Small Lymphocytic LymphomaStage II Childhood Anaplastic Large Cell LymphomaStage II Childhood Lymphoblastic LymphomaStage II Childhood Burkitt LymphomaStage III Adult Burkitt LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult Immunoblastic LymphomaStage III Adult Lymphoblastic LymphomaStage III Childhood Anaplastic Large Cell LymphomaStage III Childhood Large Cell LymphomaStage III Childhood Lymphoblastic LymphomaStage III Childhood Burkitt LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Small Lymphocytic LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Immunoblastic LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Childhood Anaplastic Large Cell LymphomaStage IV Childhood Large Cell LymphomaStage IV Childhood Lymphoblastic LymphomaStage IV Childhood Burkitt LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Small Lymphocytic LymphomaNCT00105001Fred Hutchinson Cancer Center210
已完成
3 期
Comparative Study of Modified Release (MR) Tacrolimus/Mycophenolate Mofetil (MMF) in de Novo Kidney Transplant RecipientsKidney TransplantationNCT00064701Astellas Pharma Inc668
已完成
2 期
Study Evaluating the Efficacy of Allogeneic Transplant Conditioning With Adaptive Dose Busulfan Intravenous (Busilvex®) in Patients at High Risk of Carrying Blood DiseasesHematological DiseasesNCT02483325Institut Paoli-Calmettes33
已完成
2 期
Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaChronic Lymphocytic LeukemiaRecurrent Small Lymphocytic LymphomaRefractory Chronic Lymphocytic LeukemiaStage III Chronic Lymphocytic LeukemiaStage III Small Lymphocytic LymphomaStage IV Chronic Lymphocytic LeukemiaStage IV Small Lymphocytic LymphomaT-Cell Large Granular Lymphocyte LeukemiaProlymphocytic LeukemiaNCT00104858Fred Hutchinson Cancer Center66
已完成
2 期
Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic CancerAccelerated Phase Chronic Myelogenous LeukemiaAdult Acute Lymphoblastic Leukemia in RemissionAdult Acute Myeloid Leukemia in RemissionAdult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Del(5q)Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Adult Nasal Type Extranodal NK/T-cell LymphomaAngioimmunoblastic T-cell LymphomaBlastic Phase Chronic Myelogenous LeukemiaChildhood Acute Lymphoblastic Leukemia in RemissionChildhood Acute Myeloid Leukemia in RemissionChildhood Burkitt LymphomaChildhood Chronic Myelogenous LeukemiaChildhood Diffuse Large Cell LymphomaChildhood Immunoblastic Large Cell LymphomaChildhood Myelodysplastic SyndromesChildhood Nasal Type Extranodal NK/T-cell LymphomaChronic Phase Chronic Myelogenous LeukemiaContiguous Stage II Adult Burkitt LymphomaContiguous Stage II Adult Diffuse Large Cell LymphomaContiguous Stage II Adult Diffuse Mixed Cell LymphomaContiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaContiguous Stage II Adult Immunoblastic Large Cell LymphomaContiguous Stage II Adult Lymphoblastic LymphomaContiguous Stage II Grade 1 Follicular LymphomaAnaplastic Large Cell LymphomaContiguous Stage II Grade 2 Follicular LymphomaContiguous Stage II Grade 3 Follicular LymphomaContiguous Stage II Mantle Cell LymphomaContiguous Stage II Marginal Zone LymphomaContiguous Stage II Small Lymphocytic LymphomaCutaneous B-cell Non-Hodgkin Lymphomade Novo Myelodysplastic SyndromesExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHepatosplenic T-cell LymphomaIntraocular LymphomaNodal Marginal Zone B-cell LymphomaNoncontiguous Stage II Adult Burkitt LymphomaNoncontiguous Stage II Adult Diffuse Large Cell LymphomaNoncontiguous Stage II Adult Diffuse Mixed Cell LymphomaNoncontiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaNoncontiguous Stage II Adult Immunoblastic Large Cell LymphomaNoncontiguous Stage II Adult Lymphoblastic LymphomaNoncontiguous Stage II Grade 1 Follicular LymphomaNoncontiguous Stage II Grade 2 Follicular LymphomaNoncontiguous Stage II Grade 3 Follicular LymphomaNoncontiguous Stage II Mantle Cell LymphomaNoncontiguous Stage II Marginal Zone LymphomaNoncontiguous Stage II Small Lymphocytic LymphomaNoncutaneous Extranodal LymphomaPeripheral T-cell LymphomaPreviously Treated Myelodysplastic SyndromesEssential ThrombocythemiaRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Acute Myeloid LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Myeloid LeukemiaRecurrent Childhood Anaplastic Large Cell LymphomaRecurrent Childhood Grade III Lymphomatoid GranulomatosisRecurrent Childhood Large Cell LymphomaRecurrent Childhood Lymphoblastic LymphomaRecurrent Childhood Small Noncleaved Cell LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaRecurrent/Refractory Childhood Hodgkin LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Hairy Cell LeukemiaRefractory Multiple MyelomaRelapsing Chronic Myelogenous LeukemiaSmall Intestine LymphomaSplenic Marginal Zone LymphomaStage I Adult Burkitt LymphomaStage I Adult Diffuse Large Cell LymphomaStage I Adult Diffuse Mixed Cell LymphomaStage I Adult Diffuse Small Cleaved Cell LymphomaStage I Adult Immunoblastic Large Cell LymphomaProlymphocytic LeukemiaStage I Adult Lymphoblastic LymphomaStage I Adult T-cell Leukemia/LymphomaStage I Childhood Anaplastic Large Cell LymphomaStage I Childhood Large Cell LymphomaStage I Childhood Lymphoblastic LymphomaStage I Childhood Small Noncleaved Cell LymphomaStage I Chronic Lymphocytic LeukemiaStage I Cutaneous T-cell Non-Hodgkin LymphomaStage I Grade 1 Follicular LymphomaStage I Grade 2 Follicular LymphomaStage I Grade 3 Follicular LymphomaStage I Mantle Cell LymphomaStage I Marginal Zone LymphomaStage I Multiple MyelomaStage I Small Lymphocytic LymphomaStage IA Mycosis Fungoides/Sezary SyndromeStage IB Mycosis Fungoides/Sezary SyndromeStage II Adult T-cell Leukemia/LymphomaStage II Childhood Anaplastic Large Cell LymphomaStage II Childhood Large Cell LymphomaStage II Childhood Lymphoblastic LymphomaStage II Childhood Small Noncleaved Cell LymphomaStage II Chronic Lymphocytic LeukemiaStage II Cutaneous T-cell Non-Hodgkin LymphomaStage II Multiple MyelomaStage IIA Mycosis Fungoides/Sezary SyndromeStage IIB Mycosis Fungoides/Sezary SyndromeStage III Adult Burkitt LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Adult T-cell Leukemia/LymphomaStage III Childhood Anaplastic Large Cell LymphomaStage III Childhood Large Cell LymphomaStage III Childhood Lymphoblastic LymphomaStage III Childhood Small Noncleaved Cell LymphomaStage III Chronic Lymphocytic LeukemiaStage III Cutaneous T-cell Non-Hodgkin LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Multiple MyelomaStage III Small Lymphocytic LymphomaStage IIIA Mycosis Fungoides/Sezary SyndromeStage IIIB Mycosis Fungoides/Sezary SyndromeStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Adult T-cell Leukemia/LymphomaStage IV Childhood Anaplastic Large Cell LymphomaStage IV Childhood Large Cell LymphomaStage IV Childhood Lymphoblastic LymphomaStage IV Childhood Small Noncleaved Cell LymphomaStage IV Chronic Lymphocytic LeukemiaStage IV Cutaneous T-cell Non-Hodgkin LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Small Lymphocytic LymphomaStage IVA Mycosis Fungoides/Sezary SyndromeStage IVB Mycosis Fungoides/Sezary SyndromeTesticular LymphomaUntreated Adult Acute Lymphoblastic LeukemiaUntreated Adult Acute Myeloid LeukemiaUntreated Childhood Acute Lymphoblastic LeukemiaUntreated Childhood Acute Myeloid Leukemia and Other Myeloid MalignanciesWaldenström MacroglobulinemiaPolycythemia VeraPrimary MyelofibrosisPost-transplant Lymphoproliferative DisorderNCT00089011Fred Hutchinson Cancer Center150