Phase 2 Study of Planned Donor Lymphocyte Infusion After Reduced Intensity Allogeneic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Success Rate
研究概览
简要总结
The goal of this clinical research study is to learn what dose of a kind of immune cell called T-lymphocytes (T-cells) given as a donor infusion about 8-9 weeks after a stem cell transplant has the best results. The safety of this treatment will also be studied. This will be tested in patients with leukemia, MDS, lymphoma, Hodgkin disease, and multiple myeloma. These results are measured as helping to control the disease without severe graft-versus-host disease (GvHD). GvHD is when transplanted donor tissue attacks the tissues of the recipient's body.
Fludarabine, melphalan, and alemtuzumab are commonly given before stem cell transplants:
- Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.
- Melphalan is designed to bind to the DNA of cells, which may cause cancer cells to die.
- Alemtuzumab is designed to weaken the immune system and reduce the risk of rejection of the transplant and graft-vs-host disease (GvHD).
The donor infusion of T-cells is designed to help restore the immune system after the transplant, cause an immune reaction against the cancer, and reduce the risk of the cancer coming back.
详细描述
Study Groups:
If you agree to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups involving the dose of T-cells in the donor lymphocyte infusion.
- Group 1 will receive a low dose of donor T-cells.
- Group 2 will receive a higher dose of donor T-cells than Group 1.
Both you and your study doctor will know which group you are in. Both groups will have a stem cell transplant. The stem cells will be given by vein. The cells will travel to your bone marrow where they are designed to make healthy, new blood cells after several weeks.
Study Drug Administration:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >/= 18 years and </= 65 years with one of the following: a. Acute leukemia past first remission, in first or subsequent relapse, in second or greater remission. Patients in first remission should have intermediate or high cytogenetic risk factors or flt3 mutation. Patients with primary induction failure or relapse are eligible if they have <10% bone marrow blasts, and no circulating blasts. b. Myelodysplastic syndrome with intermediate or high risk IPSS score, or treatment related MDS. c. CML resistant to tyrosine kinase inhibitor treatment in a first or subsequent chronic phase, or in accelerated phase. d. CLL, Lymphoma or Hodgkin's disease which has failed to achieve remission or recurred following initial chemotherapy. Patients must have at least a PR to salvage therapy, or low bulk untreated relapse (<2 cm largest mass). e. Multiple myeloma which has relapsed or progressed and has achieved a partial response to salvage chemotherapy.
- •Patients must have one of the following donor types identified and willing to donate: a. Related donor, HLA-matched for HLA-A, -B, C and DR matched or, b. Matched Unrelated Donor (MUD), HLA-matched for HLA A, B, C and DRB1 using allele level typing.
- •Performance score of at least 80% by Karnofsky or performance score 0 to 2 (ECOG).
- •Estimated creatinine clearance >40 ml/min (based on serum creatinine)
- •Bilirubin <1.5 mg/dl except for Gilbert's disease.
- •ALT < 300 IU/ml d.
- •Left ventricular ejection fraction equal or greater than 40%.
- •Pulmonary function test (PFT) demonstrating a diffusion capacity (corrected for hemoglobin) of least 50% predicted.
- •Patient or patient's legal representative able to sign informed consent.
排除标准
- •Patients who have had prior autologous transplants or prior allogeneic transplants are not eligible.
- •Uncontrolled active infection.
- •Positive Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
- •Women of child bearing potential not willing to use an effective contraceptive measure while on study.
- •Subject has known sensitivity to any of the products that will be administered during the study.
- •Patients who are HIV seropositive.
研究组 & 干预措施
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Fludarabine (Drug)
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Melphalan (Drug)
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Alemtuzumab (Drug)
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Stem Cell Infusion (Procedure)
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Tacrolimus (Drug)
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Methotrexate (Drug)
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: G-CSF (Drug)
Low Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Low Dose Donor T-Cells (Procedure)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Fludarabine (Drug)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Melphalan (Drug)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Alemtuzumab (Drug)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Stem Cell Infusion (Procedure)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Tacrolimus (Drug)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: Methotrexate (Drug)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: G-CSF (Drug)
High Dose Donor T-Cells
Fludarabine 40 mg/m^2 by vein on Day -6 to -3. Melphalan 140 mg/m^2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
干预措施: High Dose Donor T-Cells (Procedure)
结局指标
主要结局
Success Rate
时间窗: 100 days
Success rate defined as alive, engrafted without grade 3 or 4 GvHD or relapse at day 100 post allogeneic stem cell transplantation followed by donor lymphocyte infusion (DLI).
次要结局
- Overall Survival (OS)(Every 3 months until day of death)