A Pilot Study of Intravenous, Targeted-Dose Busulfan Monotherapy as Conditioning for Autologous Hematopoietic Progenitor Cell Transplantation in High-Risk AML
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- 100-day Non-relapse Mortality
研究概览
简要总结
During the pre-transplantation phase (following completion of consolidation chemotherapy), patients will begin to receive G-CSF at 10 mcg/kg twice daily; leukapheresis will also be given until a target goal for recipient body weight is obtained, or up to a maximum of 5 days. Conditioning/Preparative therapy will follow PBSC collection for up to 30 days with Busulfan IV daily x 4 days; subsequent doses will be adjusted based on pharmacokinetic (plasma level)monitoring. Following 1 day of rest, stem cell reinfusion will begin with supportive care. During follow-up, patients will be monitored out to 730 days.
详细描述
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Pre- Transplantation Phase -
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Twenty-four to 48 hours following completion of consolidation chemotherapy, patients will begin to receive G-CSF at 10 mcg/kg twice daily subcutaneously. Alternatively, patients may receive G-CSF alone (same dose) as mobilization therapy.
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Leukapheresis will begin day 4 of G-CSF administration and proceed according to institutional guidelines. Leukapheresis will continue until a target goal for recipient body weight is obtained, or up to a maximum of 5 days. A minimum recipient body weight is required to proceed to transplantation.
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Transplantation Phase
a. Conditioning/Preparative therapy - up to 30 days following PBSC collection, patients will begin conditioning therapy with Busulfan IV daily x 4 days (transplantation days -5,-4,-3,-2). The day -5 and -4 dose will be 130mg/m2; subsequent doses will be adjusted based on pharmacokinetic monitoring.
- Busulfan plasma level monitoring, collected around the first dose of busulfan b. Stem cell reinfusion - following 1 day of rest, previously collected autologous peripheral blood stem cells will be infused.
- The administration of supportive measures (e.g. intravenous fluids, antihistamines) during stem cell reinfusion will be performed according to institutional guidelines.
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Supportive care
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Antibiotic prophylaxis- according to hospital/institutional guidelines, and at the discretion of the treating physician.
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Growth factor support
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Transfusion support
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Prophylaxis for busulfan-induced seizures
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During follow-up, patients will be seen at least weekly for the first month and there after periodically out to 730 days posttransplant. The following medical procedures will be done:
- Medical history and physical exam (including concurrent meds, vital signs, performance status and weight)
- Standard labs
- Bone marrow aspirate and biopsy
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 56 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have had histologically confirmed diagnosis of AML, in 1st complete remission, by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute. Any induction/consolidation regimen is permitted.
- •General Inclusion Criteria:
- •Able to give informed consent
- •Hepatic and renal function: normal bilirubin, AST and ALT less than or equal to 2x normal limits, serum creatinine less than or equal to 1.5x normal
- •Left ventricular ejection fraction (LVEF) must be in normal range
- •FEV1 AND DLCO greater than or equal to 50% predicted (at planned time of transplantation)
- •ECOG PS less than or equal to 2 (at planned time of transplantation)
- •Disease Specific Inclusion Criteria:
- •Adverse-risk karyotype (del 5/5q, 7/7q, 3q, greater than or equal to 3 abnormalities):
- •Intermediate-risk karyotype [46 XY, +8, -Y, +6, or any other isolated (<3 total) non-random abnormality not included in the adverse-risk category or favorable-risk category below]
- •AML arising from antecedent hematologic disorder (e.g. MDS)
- •Secondary AML (t-AML)
排除标准
- •Acute Promyelocytic Leukemia(FAB M3) subtype
- •Presence of (8;21) translocation or inversion 16/t(16;16) cytogenetic phenotype (i.e. favorable-risk AML)
- •Eligible for and willing to undergo matched-sibling allogeneic transplantation
- •Greater than 2 induction regimens required to achieve complete remission
- •Duration of > 8 weeks between completion of induction chemotherapy and initiation of consolidation chemotherapy
- •No prior malignancy is allowed, except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least 5 years.
- •Prior extensive radiation therapy (>25% of bone marrow reserve)
- •Concomitant radiation therapy, chemotherapy, or immunotherapy
- •Intrinsic impaired organ function (as stated above)
- •Active infection
- •Positive serum pregnancy test in women who have not yet reached menopause (no menstrual periods for >12 months or who have not undergone tubal ligation or complete hysterectomy.
- •Women who are breast-feeding
- •Positive HIV testing
- •Presence of CNS leukemia
- •Uncontrolled insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal gland dysfunction
- •Physical or psychiatric conditions that in the estimation of the PI or his designee place the patient at high-risk of toxicity or non-compliance
研究组 & 干预措施
Autologous Hematopoietic Progenitor Cell Transplantation
G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion
干预措施: G-CSF (Drug)
Autologous Hematopoietic Progenitor Cell Transplantation
G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion
干预措施: Leukapheresis (Drug)
Autologous Hematopoietic Progenitor Cell Transplantation
G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion
干预措施: Busulfan (Drug)
Autologous Hematopoietic Progenitor Cell Transplantation
G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion
干预措施: Stem cell reinfusion (Procedure)
结局指标
主要结局
100-day Non-relapse Mortality
时间窗: 100 days post transplant
100-day non-relapse mortality is the number of participants who died before day 100 posttransplant from causes other than relapsed disease
次要结局
- 1 Year Event-free Survival(1 year post transplant)
- Severe Regimen-related Toxicity(up to 100 days post translant)
- Successful Autologous Stem Cell Collection(At time of stem cell collection)
- 1 Year Overall Survival(1 year post transplant)