Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients With Newly Diagnosed High-Risk Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 123
- 主要终点
- The Tolerability of BuMel Regimen
研究概览
简要总结
This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed neuroblastoma that is likely to come back or spread. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.
详细描述
PRIMARY OBJECTIVES:
I. To determine if the acute toxicity of an autologous stem cell transplant with a busulfan-melphalan (BuMel) based regimen is tolerable when given as consolidation therapy for high-risk neuroblastoma.
EXPLORATORY OBJECTIVES:
I. To determine the incidence of non-hematologic organ toxicity (grade 3 and higher) and all cause mortality in patients undergoing autologous stem cell transplant with a BuMel based regimen followed by local radiotherapy for the treatment of high-risk neuroblastoma.
II. To describe response rates, event-free survival (EFS), and overall survival (OS) for patients undergoing induction therapy followed by consolidation with myeloablative BuMel preparative regimen and local radiotherapy for the treatment of high-risk neuroblastoma.
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
- — 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria
- •Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following:
- •V-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
- •Age > 18 months (> 547 days) regardless of biologic features or
- •Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminate/unsatisfactory/unknown
- •Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following:
- •MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
- •Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
- •Patients with newly diagnosed neuroblastoma with INSS stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
- •Patients with newly diagnosed neuroblastoma with INSS stage 4S with MYCN amplification (> 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features
- •Patients >= 365 days initially diagnosed with neuroblastoma INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; study enrollment on ANBL12P1 must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S
- •Patients must not have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- •Age 1 month to < 6 months: 0.4 mg/dL
- •Age 6 months to < 1 year: 0.5 mg/dL
- •Age 1 to < 2 years: 0.6 mg/dL
- •Age 2 to < 6 years: 0.8 mg/dL
- •Age 6 to < 10 years: 1 mg/dL
- •Age 10 to < 13 years: 1.2 mg/dL
- •Age 13 to < 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females)
- •Age >= 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females)
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age
- •Shortening fraction of >= 27% by echocardiogram, or
- •Ejection fraction of >= 50% by radionuclide evaluation
- •No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible
- •Female patients who are pregnant are ineligible
- •Lactating females are not eligible unless they have agreed not to breastfeed their infants
- •Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- •Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
研究组 & 干预措施
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Pharmacological Study (Other)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Busulfan (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Cisplatin (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Cyclophosphamide (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Doxorubicin Hydrochloride (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Etoposide (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: External Beam Radiation Therapy (Radiation)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Filgrastim (Biological)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Melphalan (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Mesna (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Topotecan Hydrochloride (Drug)
Treatment (induction therapy, consolidation therapy, ASCT)
INDUCTION THERAPY:
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
The Tolerability of BuMel Regimen
时间窗: Up to 28 days post-consolidation therapy, up to 1 year
Number of patients who experience one or more unacceptable toxicities (severe sinusoidal obstruction syndrome \[SOS\] or Grade 4-5 pulmonary toxicity per Common Toxicity Criteria \[CTC\] v.4.0) during the Consolidation phase of therapy.
次要结局
未报告次要终点