An Open-label, Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of Chronic Graft Versus Host Disease After TLI/ARG Nonmyeloablative Allogeneic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Chronic Graft-vs-Host Disease (cGvHD)
研究概览
简要总结
To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)
详细描述
To test if prophylactic anti-B-cell therapy (weekly rituximab) given within 60 to 90 days after allogeneic transplantation will decrease allogeneic donor B-cell immunity and possibly the incidence of chronic graft-vs-host disease (cGvHD).
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 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between 18 and 76 years of age
- •Chronic lymphocytic leukemia (CLL):
- •Unmutated IgG VH gene status
- •Mutated IgG VH genes (> 2% nucleotide change compared to somatic sequence)
- •Complete remission benefit most from allogeneic hematopoietic stem cell transplant (HSCT).
- •(Physicians will be encouraged to provide aggressive chemotherapy prior to nonmyeloablative transplantation.)
- •Mantle cell lymphoma (MCL): Transplant physicians believe subject would benefit from allogeneic HSCT.
- •Adequate renal (Cr < 2.4 mg/dL) and hepatic (Bilirubin < 3.0 mg/dL, Aspartate aminotransferase (AST) < 100 IU) function.
- •Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
- •All subjects must provide written informed consent
- •Donor Inclusion Criteria:
- •Genotypically or phenotypically human leukocyte antigen (HLA)-identical.
- •Age < 76 unless cleared by institutional PI
- •Capable of giving written, informed consent.
- •Must consent to peripheral blood stem cell (PBSC) mobilization with G-CSF and apheresis
排除标准
- •Recipient has a 9 of 10 or 10 of 10 HLA identical donor (high resolution molecular genotyping at HLA A, B, C and DrB1, and DQ)
- •Pregnancy
- •Lactating
- •Serious uncontrolled infection
- •HIV seropositivity
- •Hepatitis B or C seropositivity
- •Cardiac function: ejection fraction < 40% or uncontrolled cardiac failure
- •Pulmonary: Diffusing capacity - carbon monoxide (DLCO) < 50% predicted
- •Liver function abnormalities: elevation of bilirubin to ≥ 3 mg/dL and/or AST > 100
- •Renal: creatinine > 2.4
- •Karnofsky performance score ≤ 60%
- •Patients with poorly controlled hypertension (systolic blood pressure > 150 or diastolic blood pressure > 90 repeatedly).
- •Known life-threatening hypersensitivity to rituximab or other anti-B cell antibodies.
- •Inability to comply with the allogeneic transplant treatment.
- •Uncontrolled central nervous system (CNS) involvement with disease
- •Donor Exclusion Criteria:
- •Identical twin to subject
- •Contra-indication to subcutaneous G-CSF at a dose of 16 mg/kg/d for 5 consecutive days
- •Serious medical or psychological illness
- •Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
- •HIV seropositivity
研究组 & 干预措施
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Total lymphoid irradiation (Procedure)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Rituximab (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Anti-thymoglobulin, rabbit (ATG, rabbit ATG) (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Cyclosporine (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Mycophenylate mofetil (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Filgrastim (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Granisetron (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Solumedrol (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Acetaminophen (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Diphenhydramine (Drug)
Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
干预措施: Hydrocortisone (Drug)
结局指标
主要结局
Chronic Graft-vs-Host Disease (cGvHD)
时间窗: 4 years
The cumulative percentage of participants who develop chronic graft-vs-host disease (cGvHD). Chronic cGvHD was defined as at least one instance of a clinically-accepted marker for cGvHD (see Filipovich, et al. Biology of Blood and Marrow Transplantation. 2005;11:945-955)
次要结局
- Incidence of Relapse(4 years)
- Mortality(Day 100 and 1 year)
- Overall Survival(4 years)
研究者
David Miklos
Assistant Professor of Medicine
Stanford University