Allogeneic Stem Cell Transplantation Followed By Adoptive Immunotherapy for Patients With Relapsed and Refractory Hodgkin's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Transplant Related Mortality Rate
研究概览
简要总结
The goal of this clinical research study is to learn if fludarabine, melphalan and gemcitabine followed by transplantation of stem cells (blood-forming cells) as well as immune cells (lymphocytes), collected from a matched related (i.e. a sibling) or unrelated donor, or a mismatched related donor, can help to control Hodgkin's disease. The safety of the treatment will also be studied.
详细描述
Central Venous Catheter:
If you choose to take part in this study, the chemotherapy, some of the other drugs in this study, and the stem cell transplant and immune cells will be given by vein through your central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
Study Drug Administration:
The days before you receive your stem cells are called minus days, such as Day -2, Day -1. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days, such as Day +1, Day +2.
On Day -7, you will receive gemcitabine by vein over about 40-180 minutes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients < 65 years of age with histologically confirmed refractory or relapsed Hodgkin's disease (including patients who fail or relapse after autologous SCT). This upper age limit will apply to transplants from both matched related and unrelated donors.
- •Patients should have any of the following disease status: a. responsive or stable disease on salvage chemotherapy or radiation therapy. b. untreated, smoldering (i.e. not rapidly progressive) relapses.
- •Patients must have a serum bilirubin equal to or </=2.0 mg/dl (isolated hyperbilirubinemia related to Gilbert's disease allowed), serum transaminase (ALT) equal to or </= 3 times the upper limit of the normal range, serum creatinine <2.0 mg/dl (provided they also have a glomerular filtration rate of at least 55 ml/min), no symptomatic cardiac or pulmonary disease and a performance status equal to or </=
- •Left ventricular ejection fraction >/= 40%, forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and corrected diffusing capacity of lung for carbon monoxide (DLCO) >/= 50% predicted.
- •Patients must have an HLA-compatible related or unrelated donor (one-antigen mismatched related donors are acceptable) willing to donate marrow or rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants from matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C, -DRB1 ("8 of 8 match") is required.
- •Women of childbearing potential must have a negative serum pregnancy test within two weeks of study entry and should be advised to avoid becoming pregnant. Men should be advised to not father a child while on treatment. Both women of childbearing potential and men must agree to practice effective methods of contraception.
- •Patients must be capable and willing to sign informed consent.
排除标准
- •Patients with documented disease progression on salvage chemotherapy.
- •Nursing or pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in the study, she should inform her treating physician immediately.
- •Severe concomitant medical or psychiatric illness.
- •Uncontrolled arrhythmia or symptomatic cardiac or pulmonary disease.
- •Chronic active hepatitis or cirrhosis.
- •Active or uncontrolled infection.
- •Radiation therapy involving chest (axilla excluded), mediastinum, or abdomen (i.e., small or large bowel) completed within 10 weeks of transplant admission. Radiation therapy shortly before the start of the preparative regimen is allowed.
- •Prior or concurrent malignancies (including myelodysplasia) except resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Protocol Chair. Cancer treated with curative intent > 5 years previously will be allowed.
研究组 & 干预措施
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Gemcitabine (Drug)
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Fludarabine (Drug)
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Melphalan (Drug)
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Antithymocyte Globulin (Drug)
Fludarabine + Melphalan
Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Melphalan (Drug)
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Allogeneic Stem Cell Infusion (Procedure)
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Tacrolimus (Drug)
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Filgrastim (G-CSF) (Drug)
Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Methotrexate (Drug)
Fludarabine + Melphalan
Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Fludarabine (Drug)
Fludarabine + Melphalan
Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Antithymocyte Globulin (Drug)
Fludarabine + Melphalan
Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Allogeneic Stem Cell Infusion (Procedure)
Fludarabine + Melphalan
Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Tacrolimus (Drug)
Fludarabine + Melphalan
Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Filgrastim (G-CSF) (Drug)
Fludarabine + Melphalan
Fludarabine 33 mg/m^2 IV for 4 days; Melphalan 70 mg/m^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Transplant Related Mortality Rate
时间窗: Transplant to 100 days post transplant
Transplant-related mortality defined as death from any cause in the first 100 days post-transplant in patients without active disease.
次要结局
未报告次要终点