A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of OTI-010 in Subjects Who Receive HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Incidence of acute GVHD grade II-IV of skin, liver and gut (stomach to rectum) through Day 84 post-PBSC transplantation
研究概览
简要总结
RATIONALE: OTI-010 may be effective for graft-versus-host disease prophylaxis (prevention) in patients who are undergoing donor peripheral stem cell transplantation for hematologic malignancies (cancer of the blood or bone marrow).
PURPOSE: This randomized phase II trial is studying how well OTI-010 works in preventing graft-versus-host disease in patients who are undergoing donor peripheral stem cell transplantation for hematologic cancer.
详细描述
OBJECTIVES:
- Compare the safety and efficacy of OTI-010 vs placebo as graft-versus-host disease prophylaxis in patients with hematologic malignancies undergoing HLA-identical sibling matched peripheral blood stem cell transplantation.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18 to 34 vs 35 to 55) and donor/recipient gender (female donor/male recipient vs female donor/female recipient vs male donor/female recipient vs male donor/male recipient).
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Conditioning regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 and undergo total body irradiation twice daily on days -3 to -1 OR busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV once daily on days -3 and -2.
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Graft-versus-host disease prophylaxis: Patients receive methotrexate IV on days 1, 3, 6, and 11. Patients also receive cyclosporine orally or IV (over 1-4 hours) twice daily beginning on day -1 and continuing for at least 6 months followed by a taper until 1 year after transplantation.
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OTI-010 therapy: Patients are randomized to 1 of 3 treatment arms.
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Arm I: Patients receive placebo IV 4 hours before peripheral blood stem cell transplantation (PBSCT) on day 0.
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Arm II: Patients receive OTI-010 IV 4 hours before PBSCT on day 0.
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Arm III: Patients receive a higher dose of OTI-010 IV 4 hours before PBSCT on day 0.
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Allogeneic stem cell transplantation: Patients undergo allogeneic PBSCT on day 0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Supportive Care
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed diagnosis of 1 of the following hematologic malignancies:
- •Acute lymphoblastic leukemia, meeting 1 of the following criteria:
- •In first or second remission
- •In early first or second relapse*
- •Acute myeloid leukemia, meeting 1 of the following criteria:
- •In first or second remission
- •In early first or second relapse*
- •Chronic myelogenous leukemia
- •Chronic or accelerated phase
- •Any of the following myelodysplastic syndromes:
- •Refractory anemia (RA)
- •RA with ringed sideroblasts
- •RA with excess blasts NOTE: *< 24% marrow blasts and < 5% peripheral blood blasts (within 10 days of beginning conditioning regimen)
- •No secondary acute leukemia
- •Prior CNS tumor involvement allowed provided patient is asymptomatic and there is no evidence of CNS disease on lumbar puncture and CT scan of the brain
- •Must have a 6/6 HLA-identical sibling donor available
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 70-100%
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Not specified
- •Bilirubin < 2 times upper limit of normal (ULN)
- •SGOT < 10 times ULN
- •Hepatitis B core antigen, surface antigen, and e-antigen negative
- •Hepatitis B DNA negative
- •Hepatitis C RNA negative
- •Creatinine clearance ≥ 60 mL/min
- •Cardiovascular
- •LVEF ≥ 50% by MUGA or echocardiogram
- •No right sided heart failure
- •FEV_1 > 50% of predicted
- •DLCO ≥ 50% of predicted (corrected for anemia)
- •Oxygen saturation ≥ 97% on room air
- •No pulmonary hypertension
- •Immunologic
- •HIV-1 and 2 antibody negative
- •HIV-1 antigen negative
- •HTLV-I and II antibody negative
- •No active infection
- •CNS function normal
- •No uncontrolled alcohol or substance abuse within the past 6 months
- •No other concurrent underlying medical condition that would preclude study participation
- •Not pregnant
- •Negative pregnancy test
- •Fertile patients must use 2 effective methods of contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- 另有 15 项未显示
排除标准
- 未提供
结局指标
主要结局
Incidence of acute GVHD grade II-IV of skin, liver and gut (stomach to rectum) through Day 84 post-PBSC transplantation
时间窗: Day 84
次要结局
- Safety as measured by infusional toxicity, relapse nd survival, formation of potential ectopic tissue foci(84 days)