Autologous Blood and Marrow Transplantation for Hematologic Malignancies and Selected Solid Tumors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 174
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)
研究概览
简要总结
This pilot trial studies different high-dose chemotherapy regimens with or without total-body irradiation (TBI) to compare how well they work when given before autologous stem cell transplant (ASCT) in treating patients with hematologic cancer or solid tumors. Giving high-dose chemotherapy with or without TBI before ASCT stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood or bone marrow and stored. More chemotherapy may be given to prepare 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. Estimate the progression free survival (PFS) distribution for Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) for each disease-specific high dose therapy regimen.
SECONDARY OBJECTIVES:
I. Estimate the PFS distribution for amyloidosis, acute leukemia and selected solid tumors for each disease-specific high dose therapy regimen.
II. Explore the role of risk factors in the outcome of all treated patients. III. Examine the high dose therapy regimen-related toxicity (RRT) and overall survival after bone marrow transplant (BMT).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of malignant hematologic disorders, amyloidosis or solid tumor malignancy
- •Recurrent or refractory disease or disease at high risk for recurrence
- •Hodgkin Disease (HL): Relapsed or refractory disease after chemotherapy with a minimum of one standard regimen
- •Non-Hodgkin Lymphoma (NHL): (Low, Intermediate or High Grade) Relapsed or refractory disease after chemotherapy with at least one standard regimen or first complete remission (CR) lymphoblastic or small, non-cleaved cell lymphoma at high risk of relapse by high International Prognostic Index (IPI) Score
- •Acute Myeloid Leukemia (AML): Low or High Risk disease in first or second CR or greater in patients in whom the risks of an allogeneic transplant outweigh the benefits
- •Acute Lymphoblastic Leukemia (ALL): Low or high risk disease in first or second CR in whom the risks of an allogeneic transplant outweigh the benefits
- •Multiple Myeloma (MM): Low or high risk in first or greater response (stable disease or better) or for responding patients at first progression
- •Other Malignant Lymphoproliferative Disorders: (chronic lymphocytic lymphoma [CLL], Waldenstroms macroglobulinemia, relapsed or refractory disease after first-line chemotherapy
- •Amyloidosis: primary or previously treated
- •Solid Tumors: Testicular cancer patients who have relapsed disease or primary progressive disease which is responding to salvage therapy; relapsed or advanced-stage newly diagnosed neuroblastoma (NBL) or small round blue cell tumors (SRBCT) in patients 30 years of age; other patients with solid tumors who have recurred following conventional treatment or are at high risk for relapse, and demonstrate chemosensitivity
- •Patients with malignancies who would be treated with an autologous stem cell transplant but have a syngeneic donor; a syngeneic donor would be considered to have the same risk as an autologous stem cell transplant patient
- •Performance status 0-2 (Karnofsky performance status [KPS] >= 70%); patients with amyloidosis or MM with decreased KPS due to disease are eligible
- •Life expectancy > 2 months
- •Pulmonary function tests; diffusing capacity of the lung for carbon monoxide (DLCO) or diffusing volume of the alveolar volume (DLVA) >= 50% predicted; DLCO to be corrected for hemoglobin and/or alveolar ventilation
- •Cardiac ventricular ejection fraction >= 50% by radionuclide ventriculogram or echocardiogram
- •Bilirubin < 3 x normal
- •Alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT) < 3 x normal
- •Calculated creatinine clearance < 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics
- •Glomerular filtration rate by renal scan for neuroblastoma patients, to determine dosing parameters
- •Positive cytomegalovirus (CMV) immunoglobulin M (IgM) and/or positive hepatitis serologies demonstrating infection will require an Infectious Disease consult and subsequent clearance
- •Any active infection will require an Infectious Disease consult and subsequent clearance
- •Peripheral Blood Counts of polymorphonuclear neutrophil (PMN) > 1500/uL
- •Platelet (Plt) > 75,000/uL
- •Prior to stem cell storage:
- •No radiation within three weeks before stem cell harvest
- •Bone marrow may be used in conjunction with blood progenitor cells
- •Hematologic Malignancy patients with human immunodeficiency virus (HIV) positivity but on appropriate anti-retroviral therapy may go autotransplant with the following laboratory tests; (CD4+ cell count > 75 cells per microliter and HIV copy number < 100,000 per microliter and with Infectious Disease clearance
- •Acute Leukemia, HL, NHL, MM and Solid Tumor patients must have received 2 cycles of chemotherapy followed by disease-specific restaging prior to mobilization and collection of stem cells; small round blue cell tumor patients must have received either standard therapy or surgical intervention; the disease status and response to therapy must be known prior to transplant to establish the disease status at transplant; amyloidosis patients may proceed to BMT without receiving chemotherapy
- •No serious organ dysfunction unless it is caused by the underlying disease, exclusion criteria include the following:
- •Uncontrolled or severe cardiovascular disease, including recent (< 6 months) myocardial infarction, congestive heart failure, symptomatic angina, life-threatening arrhythmia or hypertension
- •Active bacterial, viral, or fungal infection
- •Active peptic ulcer disease
- •Uncontrolled diabetes mellitus
- •No serious medical or psychiatric illness
- •Not pregnant
- •No psychiatric conditions which would prevent delivery of care; psychology clearance is necessary
- •Allogeneic BMT not possible, or not desirable
- •Age > 65 years
- •No compatible donor identified
- •Estimated risk of graft vs. host disease complications greater than risk of recurrence after autologous BMT
- •Adequate bone marrow or blood stem cell dose obtained:
- •For blood stem cells: total CD 34+ >= 2 x 10^6/kg or if unable to collect this dose, a total nucleated cell bone marrow dose of >= l x 10^8/kg
排除标准
- 未提供
研究组 & 干预措施
Regimen CBV (patients with HL or NHL)
Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
干预措施: etoposide (Drug)
Regimen CBV (patients with HL or NHL)
Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
干预措施: cyclophosphamide (Drug)
Regimen CBV (patients with HL or NHL)
Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
干预措施: carmustine (Drug)
Regimen CBV (patients with HL or NHL)
Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
干预措施: autologous hematopoietic stem cell transplantation (Procedure)
Regimen M200/M120 (patients with MM or amyloidosis)
Patients receive 200 or 120 mg/m^2 of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.
干预措施: melphalan (Drug)
Regimen M200/M120 (patients with MM or amyloidosis)
Patients receive 200 or 120 mg/m^2 of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.
干预措施: autologous hematopoietic stem cell transplantation (Procedure)
Regimen BuC2iv (patients with ALL, AML, HL, or NHL)
Patients receive busulfan IV over 2 hours then every 6 hours on days -7 to -4 for 16 total doses and cyclophosphamide IV over 2 hours on days -3 and -2. Patients undergo ASCT on day 0.
干预措施: cyclophosphamide (Drug)
Regimen BuC2iv (patients with ALL, AML, HL, or NHL)
Patients receive busulfan IV over 2 hours then every 6 hours on days -7 to -4 for 16 total doses and cyclophosphamide IV over 2 hours on days -3 and -2. Patients undergo ASCT on day 0.
干预措施: busulfan (Drug)
Regimen BuC2iv (patients with ALL, AML, HL, or NHL)
Patients receive busulfan IV over 2 hours then every 6 hours on days -7 to -4 for 16 total doses and cyclophosphamide IV over 2 hours on days -3 and -2. Patients undergo ASCT on day 0.
干预措施: autologous hematopoietic stem cell transplantation (Procedure)
Regimen CT6 (patients with ALL)
Patients receive cyclophosphamide IV over 2 hours on days -5 to -4. Patients then undergo TBI twice daily on days -3 to -1. Patients undergo ASCT on day 0.
干预措施: cyclophosphamide (Drug)
Regimen CT6 (patients with ALL)
Patients receive cyclophosphamide IV over 2 hours on days -5 to -4. Patients then undergo TBI twice daily on days -3 to -1. Patients undergo ASCT on day 0.
干预措施: total-body irradiation (Radiation)
Regimen CT6 (patients with ALL)
Patients receive cyclophosphamide IV over 2 hours on days -5 to -4. Patients then undergo TBI twice daily on days -3 to -1. Patients undergo ASCT on day 0.
干预措施: autologous hematopoietic stem cell transplantation (Procedure)
Regimen CTtCp (patients with other solid tumors)
Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
干预措施: cyclophosphamide (Drug)
Regimen VCp (patients with testicular cancer)
Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients then undergo a second ASCT on day 0.
干预措施: carboplatin (Drug)
Regimen CTtCp (patients with other solid tumors)
Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
干预措施: carboplatin (Drug)
Regimen CTtCp (patients with other solid tumors)
Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
干预措施: thiotepa (Drug)
Regimen CTtCp (patients with other solid tumors)
Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
干预措施: autologous hematopoietic stem cell transplantation (Procedure)
Regimen VCp (patients with testicular cancer)
Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients then undergo a second ASCT on day 0.
干预措施: etoposide (Drug)
Regimen VCp (patients with testicular cancer)
Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients then undergo a second ASCT on day 0.
干预措施: autologous-autologous tandem hematopoietic stem cell transplantation (Procedure)
Regimen TtC1500/ECpM (patients with NBL or SRBCT)
Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
干预措施: etoposide (Drug)
Regimen TtC1500/ECpM (patients with NBL or SRBCT)
Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
干预措施: cyclophosphamide (Drug)
Regimen TtC1500/ECpM (patients with NBL or SRBCT)
Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
干预措施: melphalan (Drug)
Regimen TtC1500/ECpM (patients with NBL or SRBCT)
Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
干预措施: carboplatin (Drug)
Regimen TtC1500/ECpM (patients with NBL or SRBCT)
Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
干预措施: thiotepa (Drug)
Regimen TtC1500/ECpM (patients with NBL or SRBCT)
Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
干预措施: autologous-autologous tandem hematopoietic stem cell transplantation (Procedure)
结局指标
主要结局
Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)
时间窗: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years
Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed.
次要结局
- Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors)(Patients are followed up to maximum of 12 years)
- Regimen-related Toxicity Grade 2-4 in Any Organ (Measured by Bearman Score, Values Range From 0 (None) to 4 (Fatal))(Up to 100 days after transplantation)
- Response Rate (Complete Remission)(At 100 days)