A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 6
- 主要终点
- Complete Response Rate
研究概览
简要总结
RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.
详细描述
OBJECTIVES:
- Determine the complete response rate in patients with myelodysplastic syndromes treated with reduced-intensity allogeneic bone marrow transplantation, including photopheresis, total body irradiation, and pentostatin.
- Determine the disease-free and overall survival of patients treated with this regimen.
- Determine the engraftment rate of donor cells in patients treated with this regimen.
- Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a single-arm, two-stage, multicenter phase II study.
- Preparative Regimen: Patients undergo photopheresis using methoxsalen on days -7 and -6 and receive pentostatin intravenously (IV )continuously on days -5 and -4. Total body irradiation is administered on days -3 and -2 for a total of 3 doses.
- Transplantation: Allogeneic bone marrow or peripheral blood stem cells are infused on day 0.
- Acute graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV on days -1 to 30 and then orally every 12 hours. Cyclosporine dose is then tapered beginning after day 50 and continuing for 6 months in the absence of GVHD. Once cyclosporine dose is significantly decreased, oral mycophenolate mofetil (MMF) is then administered twice a day. MMF dose is then tapered for 12 months in the absence of GVHD. Patients also receive methotrexate IV on days 1 and 3.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •One of the following cytologically proven myelodysplastic syndromes
- •Refractory anemia (RA)
- •RA with ringed sideroblasts
- •RA with excess blasts
- •Chronic myelomonocytic leukemia
- •International Prognosis Scoring System (IPSS) score of at least 0.5 OR red cell transfusion dependence for at least 6 months (2 units per month)
- •Patients with an IPSS score less than 0.5 may be eligible provided they previously had a higher IPSS score and received chemotherapy at that time
- •Suitable human leukocyte antigen (HLA)-matched donor (related or unrelated) available
- •No cord blood donors
- •Related donors must be genotypically matched (HLA A, B and DR) at 5/6 or 6/6 loci and may be a sibling, parent, or child
- •Unrelated donors must have high resolution typing done at A, B, C and DR, and must be matched at all or may have a single antigen or allele mismatch at no more than one of these loci
- •Patients must have < 20% blasts on bone marrow study within 1 month of study entry
- •Age of 18 to 70 years
- •Eastern Cooperative Oncology Group performance status 0-1
- •Life expectancy at least 6 months
- •At least 90 days since prior autologous bone marrow transplantation
- •Serum erythropoietin level greater than 100 for patients who have not received a prior course of epoetin alfa
- •No iron deficiency
- •Iron deficiency anemia treated with iron replacement therapy allowed
- •Bilirubin less than 2.0 mg/dL
- •Alkaline phosphatase less than 2 times upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times ULN
- •Creatinine less than 2.0 mg/dL OR creatinine clearance greater than 50 mL/min
- •Left ventricular ejection fraction (LVEF) at least 45% by Multigated Acquisition scan (MUGA) or echocardiogram
- •Carbon Monoxide Diffusing Capacity (DLCO) at least 50% of predicted (corrected for hemoglobin)
- •Forced expiratory volume in 1 second (FEV_1) at least 50% of predicted
- •Recovered from prior chemotherapy
- •Physically and psychologically capable of undergoing study regimen
- •Able to receive 600 cGy of total body irradiation
- •HIV negative
- •Negative pregnancy test
排除标准
- •Pregnant or nursing
- •Having other medical condition that would reduce life expectancy
- •Active ongoing infection
- •Prior myeloablative or nonmyeloablative allogeneic transplantation for Myelodysplastic syndrome or acute myeloid leukemia
研究组 & 干预措施
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: Cyclosporine (Drug)
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: Methotrexate (Drug)
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: Photopheresis (Drug)
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: Mycofenolate mofetil (Drug)
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: Pentostatin (Drug)
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: allogeneic bone marrow (Procedure)
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: peripheral blood stem cell (Procedure)
Arm I
Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.
Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.
Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
干预措施: Total body irradiation (Radiation)
结局指标
主要结局
Complete Response Rate
时间窗: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.
Completed response is defined as: Bone marrow evaluation: Repeat bone marrow showing \< 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia (see dysplasia qualifier under peripheral blood evaluation). Peripheral blood evaluation \[absolute values must last at least 2 months\] Hemoglobin \>11 g/dl (untransfused, not on erythropoietin) Neutrophils (1500/mm3 (not on a myeloid growth factor)) Platelets (100,000/mm3 (not on a thrombopoetic agent)) Blasts - 0% No dysplasia. No detectable cytogenetic abnormality, if preexisting abnormality was present
次要结局
- Overall Survival(Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.)
- Time to Engraftment for Neutrophil(Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.)
- Time to Engraftment for Platelet(Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.)
- Number of Patients Who Developed Disease Progression After Achieving Complete Response(Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.)
- Proportion of Graft Versus Host Disease(Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.)