Allogeneic Peripheral Blood Stem Cell Transplantation With Minimally Myelosuppressive Regimen of Pentostatin and Low-dose Total-body Irradiation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting
研究概览
简要总结
This is a continuation of a pilot study which is now regarded as a phase II trial with a plan to enroll an additional 40 patients (20 related and 20 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive regimen with pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT).
详细描述
This is a pilot study which began with a plan to enroll 50 patients (20 related and 30 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive regimen with Pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT). Patients with persistent or progressive malignancy after transplantation will be treated with GM-CSF (cytokine therapy) to assess its toxicity and potential therapeutic efficacy. Patients with persistent or progressive disease who fail or do not qualify for the cytokine therapy portion of the study will become candidates for donor leukocyte infusions.
The purpose of this protocol remains a pilot study which is now regarded as a phase II trial with a plan to enroll 40 ADDITIONAL patients (20 related and 20 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a modified version of the original preparative regimen of Pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT). Patients who fail will become candidates for donor-leukocyte infusion (DLI).
Primary Objectives
- To determine the safety of treating hematological malignancies by establishing donor hematopoietic chimerism using pentostatin and low-dose total body irradiation followed by allogeneic peripheral blood stem cell transplantation.
- To determine the immunomodulatory effects of pentostatin as part of the conditioning regimen for allogeneic peripheral blood stem cell transplantation.
Secondary Objectives
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
- 19 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 19-75 years
- •Patients who relapse after autologous stem cell transplantation.
- •Patients who are candidates for an autologous or conventional allogeneic stem cell transplantation from a disease standpoint but who do not qualify functionally (from the point of view of organ function, or performance status) for a myeloablative protocol.
- •Any patient, where in the opinion of the primary treating oncologist, nonmyleoablative therapy would be the treatment option in the best patients interest providing the patient fits all other eligibility criteria for this protocol.
- •Identification of a matched related or unrelated stem cell donor
- •Acute myelogenous leukemia first complete remission with high-risk cytogenetics>second complete remission minimal residual disease (<10% blasts*). Acute lymphocytic leukemia first complete remission with high-risk cytogenetics >second complete remission minimal residual disease (<10% blasts*). Chronic myelogenous leukemia first chronic phase, accelerated phase (<10% blasts*)blast phase with minimal residual disease (<10% blasts*)second chronic phase. Chronic lymphocytic leukemia recurrence after the front line regimen (related donor transplant), chemorefractory disease (unrelated donor transplant),T-CLL in partial remission or any minimal residual disease. Myelodysplastic syndromes refractory anemia with or without ringed sideroblasts,RAEB, RAEB-T, and CMML (< than 10% blasts*). *both in peripheral blood and bone marrow
- •Multiple myeloma - after receiving at least one regimen of prior chemotherapy
- •Non-Hodgkin's Lymphomas:
- •Small Lympho(plasma)cytic Lymphoma (B-SLL, B-LPL): recurrence after a front line regimen (related donor transplant), or chemorefractory disease (related or unrelated donor transplant). Follicular Low-Grade Lymphoma, Marginal Zone Lymphomas (splenic, nodal, or extranodal/MALT type): chemorefractory disease or > 2 prior regimens. Mantle Cell Lymphoma: first complete or partial remission, refractory disease, or failed prior ASCT. Diffuse Large B-cell Lymphoma, Follicular Large cell Lymphoma, Peripheral T-cell Lymphoma, Anaplastic Large Cell Lymphoma: refractory disease, or failed prior ASCT. Burkitt or Acute Lymphoblastic Lymphomas: high-risk disease in remission, chemosensitive persistent or recurrent disease. Cutaneous T-cell Lymphomas: (Mycosis Fungoides, Sezary Syndrome): chemorefractory disease of > 2 prior regimens
- •Hodgkins Disease: refractory or persistent disease and not candidate for ASCT, or failed prior ASCT.
- •Peripheral T-cell Lymphoma
排除标准
- •Age > 75 years and < 19 years
- •progressive disease within 8 weeks of prior therapy or within 12 weeks after prior autologous stem cell transplantation
- •Active CNS malignancy (patients with known positive CSF cytology or parenchymal lesions visible by CT or MRI)
- •Fertile men or women unwilling to use appropriate contraceptive techniques during and for 12 months following treatment
- •Females who are pregnant
- •Patients who are HIV seropositive
- •Active uncontrolled infection or immediate life-threatening condition at the time of enrollment
- •Significant Organ dysfunction:
- •Calculated Creatinine Clearance <55ml/min
- •cardiac ejection fraction <40%, NYHA class II or greater cardiac disease.
- •DLCO < 40% , FEV1/FVC ratio <50% predicted, or receiving supplementary continuous oxygen
- •total bilirubin > 2x upper limit of normal (unless due to Gilberts disease or malignancy), ALT and AST 4x the upper limit of normal
- •Karnofsky score <60%
- •Patients with uncontrolled medical illnesses (e.g., uncontrolled systemic hypertension, diabetes)
- •Donor Inclusion Criteria:
- •HLA genotypically matched relative
- •siblings or first-degree relatives matched at HLA-A, B, or DR loci (6 antigen match) are acceptable donors
- •HLA matched unrelated volunteer donor
- •unrelated donor matched at HLA-A, B, or DR loci (6 antigen match) are acceptable donors
- •One antigen mismatch related or unrelated donor will also be acceptable, molecular typing needs to be used at each H LA-A, B, or DR loci in case of mismatched unrelated donor.
- •Donor Exclusion Criteria:
- •Identical twin
- •Pregnancy
- •HIV positive
- •Serious Allergy to G-CSF
- •Current serious systemic illness
- •Failure to meet the UNMC or NMDP criteria for donors
研究组 & 干预措施
Cohort I
Pentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day
干预措施: Pentostatin (Drug)
Cohort I
Pentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day
干预措施: Total-body irradiation (TBI) (Radiation)
Cohort I
Pentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day
干预措施: Cyclosporine A (CsA) (Drug)
Cohort I
Pentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day
干预措施: Mycophenolate Mofetil (MMF) (Drug)
Cohort I
Pentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day
干预措施: G-CSF (Drug)
结局指标
主要结局
Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting
时间窗: days +28 and +70
the efficacy of the regimen as determined by engraftment rate and establishment of donor hematopoietic chimerism at day +28 and day +70.
Toxicity for the Combination of Pentostatin and Low Dose Total Body Irradiation (TBI)
时间窗: Conditioning regimen to count recovery (D + 28 post transplant)
次要结局
- Incidence of Acute and Chronic Graft-versus-host Disease(twice weekly until day 100 up to 1 year post transplant)
- Responses to Therapy(every 6 mo. up to 2 years)
- Kinetics of Immunologic Reconstitution(at day 100 post transplantation)