NCT00874315撤回2 期
A Multicenter Pilot Study of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation With In-vivo T-cell Depletion to Evaluate the Role of NK Cells and KIR Mis-matches in Relapsed or Refractory High-risk Neuroblastoma.
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 4
- 主要终点
- Feasibility as measured by the incidence of donor engraftment, transplant-related mortality, and grade III-IV acute graft-vs-host disease (GVHD) at day 100 and the incidence of extensive chronic GVHD within the first year post-transplantation
研究概览
简要总结
RATIONALE: - Relapsed or refractory Neuroblastoma (NBL) carries a very poor prognosis and children with relapsed NBL have an overall 3 year survival rate of < 10%. Hematopoietic Stem Cell Transplant from a different donor (allogeneic), is a form of adoptive cellular therapy , such that infused donor cells find host tumors as foreign and fight them. After transplant, the donor immune cells (i.e. T cells, NK cells) mediate Graft versus Tumor (GVT) effect and may stop tumor from recurring. Also,reduced intensity transplants lead to minimal toxicity and less risk of mortality in heavily pre-treated NBL patients.
PURPOSE: This phase II trial is studying how well giving a reduced intensity(using Fludarabine, Busulfan and antithymocyte globulin)preparative regimen followed by donor stem cell transplant works in treating young patients with high-risk neuroblastoma that has relapsed or not responded to treatment.
详细描述
OBJECTIVES:
Primary
- To determine the feasibility of allogeneic hematopoietic stem cell transplantation after a reduced-intensity conditioning regimen comprising fludarabine phosphate, busulfan, and anti-thymocyte globulin, in terms of donor engraftment, transplant-related mortality, and development of acute and chronic graft-vs-host disease, in pediatric patients with high-risk relapsed or refractory neuroblastoma.
Secondary
- To elucidate the role of natural killer (NK) cells as effectors of graft-vs-tumor effect in these patients.
- To evaluate the role of killer immunoglobulin-like receptor (KIR) mismatches in the donor-recipient pairs on the outcomes of these patients.
- To determine the incidence of progression-free survival at 1 year post-transplantation in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of high-risk neuroblastoma, meeting one of the following criteria:
- •Refractory disease, defined as no response, mixed response, or progressive disease after completion of induction therapy administered according to clinical trials COG-A3973 or COG-ANBL0532 (or other similar high-intensity induction regimen)
- •Relapsed following high-dose chemoradiotherapy including autologous stem cell transplantation
- •Achieved a complete remission (CR), very good partial remission (VGPR), or partial remission (PR) after ≤ 2 different salvage regimens, as defined by the following:
- •In CR after treatment with some form of salvage therapy (e.g., ¹³¹I-MIBG, antibody-based therapy, or any other COG or NANT salvage-therapy regimen)
- •In VGPR or PR after salvage therapy
- •No more than 3 sites of skeletal disease as determined by an ¹²³I-MIBG scan (for regional involvement of the skeleton [e.g., pelvis, spine], the tumor involvement should be < 25% of the site)
- •Bone marrow involvement (< 25% neuroblasts) by morphologic exam within the past 2 weeks
- •Patients with soft tissue disease are eligible provided they exhibit either a VGPR or PR in the primary soft tissue mass and in any sites of metastatic soft tissue disease
- •Disease status meeting one of the following criteria:
- •Minimal residual disease
- •Disease considered responsive to a salvage regimen
- •Stable disease
- •No rapidly progressive disease
- •Donors must meet one of the following criteria:
- •Matched, related donor (6/6 or 5/6) (bone marrow donor allowed)
- •HLA-matched unrelated donor (10/10 match on high-resolution [HR] typing of HLA-A, B, C, DRB1, and DQB1)
- •One allele- or antigen-mismatched unrelated donor (9/10 match on HR typing), mismatched at HLA-C only
- •One allele- or antigen-mismatched unrelated donor (9/10 match on HR typing), mismatched at HLA-A, B, DRB1, or DQB1 (only when HLA-C mismatch is not available)
- •PATIENT CHARACTERISTICS:
- •Karnofsky/Lansky performance status 60-100%
- •ANC > 500/mm^3
- •Creatinine clearance or radioisotope GFR ≥ 60 mL/min
- •Total bilirubin < 3.0 mg/dL
- •AST or ALT < 5 times upper limit of normal
- •Shortening fraction ≥ 25% by ECHO OR ejection fraction > 30% by MUGA
- •FEV_1 and DLCO ≥ 30% OR normal chest x-ray, pulse oximetry, and venous blood gas
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV negative
- •No active or recent (within the past 30 days) fungal infection
- •No proven or suspected sepsis, pneumonia, or meningitis unless appropriate therapeutic measures have been initiated to control the infection and systemic signs are no longer life-threatening
- •No requirement for oxygen or ventilator support
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Prior tandem autologous stem cell transplantations (according to clinical trial COG-ANBL0532) allowed
- •No prior allogeneic hematopoietic stem cell transplantation
- •More than 2 months since prior autologous stem cell transplantation, myeloablative therapy, total-body irradiation, whole abdominal radiotherapy, or therapeutic ¹³¹I-MIBG
- •More than 3 weeks since prior chemotherapy, immunotherapy (including anti-GD2 regimen), or biologic response modifiers and recovered
- •More than 2 weeks since prior local radiotherapy to the sites of metastatic disease
排除标准
- 未提供
结局指标
主要结局
Feasibility as measured by the incidence of donor engraftment, transplant-related mortality, and grade III-IV acute graft-vs-host disease (GVHD) at day 100 and the incidence of extensive chronic GVHD within the first year post-transplantation
时间窗: 100 days post-HSCT
The safety and feasibility of reduced intensity allogeneic HSCT will be established in this population by monitoring the incidence of adverse events- 100 day mortality,incidence of severe acute GVHD and non-engraftment of donor cells.
次要结局
- Progression-free survival (PFS) at 1 year(1 year post- HSCT)
- Relationship between biologic endpoints (e.g., number of natural killer [NK] cells infused, NK cell recovery, and NK cell chimerism status) and clinical endpoints (e.g., donor engraftment, acute GVHD, transplant-related mortality, and PFS)(3 and 6 months post-SCT)
- Relationship between presence of killer immunoglobulin-like receptor (KIR) mismatches and clinical endpoints(3 and 6 months post-HSCT)
研究者
研究点 (4)
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