Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Number of Participants With Absolute Neutrophil Count Engraftment
研究概览
简要总结
Donor:
This clinical study will evaluate the feasibility of a purified CD34 peripheral blood progenitor cell (PBPC) transplants in patients with hematological malignancies.
The primary objectives of the study are to evaluate the recipient obtaining donor derived neutrophil engraftment and the incidence of acute graft versus host disease [GvHD] (grade III-IV).
Secondary objectives include assessments of recipient having donor derived platelet engraftment, incidence of graft failure and chronic GvHD, overall and disease free survival, clinical safety and device performance of the CliniMACS CD34 selection device.
详细描述
Donor Description:
Before taking part in this study, donors will have an evaluation that is the standard for any bone marrow or blood stem cell donor. These include standard blood tests, an electrocardiogram (EKG), and a chest X-ray. Donors will also be given a general health questionnaire that is given to all blood donors in the United States. It should take no more than 10 minutes to complete the questionnaire.
Donors in this study will receive standard mobilization therapy with daily G-CSF every 12 hours. The Granulocyte colony-stimulating factor (G-CSF) will be given as an injection under the skin. The mobilization phase starts on the first day that donors receive G-CSF and continues until the final day of the stem cell collection process (leukapheresis).
Donors in this study will receive Neupogen (white blood cell growth factor) to stimulate the immature blood cells. They will receive two injections, twice a day for four days. On the fourth day, assuming they have enough immature white blood cells, researchers will start the stem cell collection process (leukapheresis).
The stem cell collection will go from 1 to 4 days until enough immature cells have been collected, but will not be done on any day the donor's platelet count falls below 75,000. The stem cell is called a CD34(+) cell. These cells will then be processed over a cell-processing machine to try to purify the immature fraction of cells and remove the T-lymphocytes that are part of the fatal graft versus host disease. The T-cell is called a CD3(+) cell.
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
- — 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female recipients must have histopathologically confirmed diagnosis of hematological or lymphatic malignancy in one of the following categories:
- •Acute Leukemia: Recipients must have acute leukemia in second or greater remission in relapse, or primary refractory disease. Acute leukemia (in first remission with poor risk factors and molecular prognosis; acute myelogenous leukemia (AML) with -5, -7, t(6:9), +8, -11q23 and Acute lymphoblastic leukemia (ALL) with Phil+ t(9:22), t(4:11) and secondary remission inclusive).
- •Chronic myelogenous leukemia: Chronic Myeloid Leukemia (CML) in accelerated phase, blast crisis or second chronic phase.
- •Myelodysplastic syndrome (in high and intermediate risk categories) - marrow blast > 10% on differential.
- •Non-Hodgkin's lymphoma in relapse
- •Refractory chronic lymphoid leukemia (CLL) - refractory to fludarabine based regimen, unrelated donor and haploidentical only
- •The recipient must be <=60 years old at time of registration.
- •The recipient must have a related donor haploidentical for human leukocyte antigen (HLA), A, B, C, or DR loci. They may be partial matched on the other haplotype.
- •Recovery from prior therapy, chemotherapy, or radiotherapy, as defined by: Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2; have recovered from the toxicity of prior major chemotherapy at the start of the preparative regimen on this protocol
- •Adequate cardiac and pulmonary function (Left ventricular ejection fraction (LVEF) >45%, Carbon Monoxide Diffusing Capacity (DL CO)>50% corrected for hemoglobin)
- •Serum creatinine <1.5 mg/dL or creatinine clearance >50 ml/min for those above serum creatinine of 1.5; serum bilirubin <2.0 mg/dL; Aspartate transaminase (AST)/alanine aminotransferase (ALT) <2* Upper limits of normal (ULN) (unless secondary to disease)
- •Females of childbearing potential must have a negative serum or urine beta-HCG test within three weeks of registration. Patients will be informed of the risk of not receiving adequate contraception.
- •No prior cancer within five years with the exception of surgically cured non-melanoma skin cancer or in situ cancer of the cervix
- •The recipient and/or the recipient's legal guardian must have been informed of the investigational nature of this study and have signed a consent form which is in accordance with Federal guidelines and the guidelines of the participating institution.
- •Donor age must be 4-80 years and weight greater than 20 kg.
- •Medical history and physical examination confirm good health status as defined by institutional standards
- •Seronegative for HIV Ag, HIV 1+2 Ab, Human T Cell Leukemia Virus (HTLV) I/II Ab, HbsAg, HbcAb (IgM [combination screening test] and IgG), HCV, RPR for syphilis within 30 days of apheresis collection - If positive for Hepatitis B or C or syphilis, the recipient must be notified - the recipient may proceed if PI, recipient and donor agree and there is no substitute donor
- •HLA matching criteria
- •Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization
- •Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate
- •Agreeable to second donation of PBPC (or a bone marrow harvest) should the patient fail to demonstrate sustained engraftment following the transplant
- •The donor, or legal guardian greater than 18 years of age, must have been informed of the investigational nature of this study and have signed a consent form in accordance with Federal Guidelines and the guidelines of the participating institution. If the donor is less than 18 years of age, parent or legal guardian consent must be obtained.
- •The prospective donor will be screened for cytomegalovirus (CMV) seroreactivity and a seronegative donor will be utilized if available when the patient is seronegative.
排除标准
- •Participation in other clinical trials which involve investigational drugs or devices that might influence the endpoints of this study
- •Evidence of active hepatitis (B and/or C) or cirrhosis
- •Neither the recipient nor the donor may be HIV positive
- •Presence of any other active, uncontrolled bacterial, viral or fungal infection.
- •Uncontrolled central nervous system (CNS) involvement with tumor cells
- •Documented allergy to murine proteins or iron dextran
- •The recipient is a lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control.
- •Severe end-organ dysfunctions, particularly neurologic deficits detectable by clinical examination or significant intellectual impairment in metabolic disorders
- •Evidence of active infection (including urinary tract infection, or upper respiratory tract infection) or hepatitis (on screening).
- •Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.
- •Factors that place the donor at increased risk for complications from leukapheresis or G-CSF therapy such as pulmonary hypertension, coronary artery disease, peripheral vascular disease, cerebral vascular disease.
- •Lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control.
- •Donors who are hepatitis positive, Human T-cell lymphotropic virus type I (HTLVI) positive need consent of Principal Investigator and determination that this is the best donor.
研究组 & 干预措施
CD34 PBPC
CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
干预措施: Megadose of CD34 Selected Progenitor Cells (Procedure)
CD34 PBPC
CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
干预措施: Melphalan (Drug)
CD34 PBPC
CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
干预措施: Thiotepa (Drug)
CD34 PBPC
CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
干预措施: Fludarabine (Drug)
CD34 PBPC
CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
干预措施: Rabbit ATG (Drug)
结局指标
主要结局
Number of Participants With Absolute Neutrophil Count Engraftment
时间窗: Day 0 up to Day 30
Absolute neutrophil engraftment defined as first of 3 consecutive days with Absolute neutrophil count (ANC) equal to or more than 0.5 \* 10\^9/L. Baseline to Day 30 post transplant.
次要结局
未报告次要终点