Phase I-II Study of Escalating Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy in Combination With Etoposide (VP16) and Cytoxan as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation for Patients With Poor Risk Acute Lymphocytic Leukemia (ALL) or Poor Risk Acute Myelogenous Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose of Intensity-modulated Radiotherapy (Phase I)
研究概览
简要总结
RATIONALE: Giving intensity modulated radiation therapy (IMRT) and chemotherapy, such as etoposide and cyclophosphamide, before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving IMRT together with chemotherapy before transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects and best dose of intensity-modulated radiation therapy (IMRT) when given together with etoposide and cyclophosphamide followed by donor stem cell transplant and to see how well they work in treating patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).
详细描述
OBJECTIVES: I. To establish the maximum tolerated dose [MTD] of large field image-guided IMRT, using helical tomotherapy when given in combination with intravenous cyclophosphamide and VP-16 as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical sibling or unrelated donor in patients with ALL or AML with induction failure or in relapse. (Phase I) II. To describe the toxicity at each dose level standard. (Phase I) III. To collect data on the radiation dose to normal organs and bone marrow using tomotherapy targeted total-body irradiation (TBI). (Phase I) IV. To estimate the overall survival probability, disease free survival probability and relapse rate associated with this regimen. (Phase II) V. To characterize the treatment related mortality and toxicity profile (early/late) associated with this regimen. (Phase II) VI. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population conditioned with whole body radiation. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy (IMRT) followed by a phase II study.
PREPARATIVE REGIMEN: Patients undergo IMRT using helical tomotherapy once or twice daily on days -10 to -6 or -10 to -7. Patients also receive etoposide intravenously (IV) on day -6 or -5 and cyclophosphamide IV on day -4 or -3.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day -1 or day 0. After completion of study treatment, patients are followed up periodically for up to 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with acute lymphocytic leukemia or acute myelogenous leukemia who are not in first or second remission (i.e., after failing remission induction therapy or in relapse or beyond second remission)
- •All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical sibling who is willing to donate bone marrow or primed blood stem cells or a 10/10 allele matched unrelated donor; a single allele mismatch at A, B, C, DR, or DQ and a KIR mismatch at C will be allowed; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques
- •Prior therapy with VP-16, Busulfan, and Cytoxan is allowed
- •A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of >= 50% established by multi gated acquisition scan (MUGA) or echocardiogram
- •Patients must have a serum creatinine of less than or equal to 1.2 or creatinine clearance > 80 ml/min
- •A bilirubin of less than or equal to 1.5
- •Serum glutamic oxaloacetic transaminase (SGOT) less than 5 times the upper limit of normal
- •Serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal
- •Pulmonary functioning tests including diffusing capacity of carbon monoxide (DLCO) will be performed; forced expiratory volume in one second (FEV1) and DLCO should be greater than 50% of the predicted normal value
- •The time from the end last induction or reinduction attempt should be >= 14 days
- •Signed informed consent form approved by the Institutional Review Board (IRB) is required
- •DONOR: Any sibling donors who are histocompatible with the prospective recipient will be considered a suitable donor
- •Donors will be excluded if for psychological or medical reasons they are unable to tolerate the procedure
- •Donor should be able to donate peripheral blood stem cells or bone marrow
排除标准
- •Prior radiation therapy that would exclude the use of total-body irradiation
- •Patients who have undergone bone marrow transplantation previously and who have relapsed
- •Patients with psychological or medical condition that patients physician deems unacceptable to proceed to allogeneic bone marrow transplant
- •Pregnancy
- •Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction < 50%
研究组 & 干预措施
Level 4: 1500cGy limited dose to liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: etoposide (Drug)
Level 1: 1200cGy
150cGy BID x Days 1-4. Total dose 1200cGy.
干预措施: etoposide (Drug)
Level 2: 1350cGy
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
干预措施: etoposide (Drug)
Level 2: 1350cGy
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 4: 1500cGy limited dose to liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: cyclophosphamide (Drug)
Level 1: 1200cGy
150cGy BID x Days 1-4. Total dose 1200cGy.
干预措施: cyclophosphamide (Drug)
Level 1: 1200cGy
150cGy BID x Days 1-4. Total dose 1200cGy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 1: 1200cGy
150cGy BID x Days 1-4. Total dose 1200cGy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 1: 1200cGy
150cGy BID x Days 1-4. Total dose 1200cGy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 1: 1200cGy
150cGy BID x Days 1-4. Total dose 1200cGy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 1: 1200cGy
150cGy BID x Days 1-4. Total dose 1200cGy.
干预措施: tomotherapy (Radiation)
Level 2: 1350cGy
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
干预措施: cyclophosphamide (Drug)
Level 2: 1350cGy
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 2: 1350cGy
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 2: 1350cGy
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 2: 1350cGy
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
干预措施: tomotherapy (Radiation)
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: cyclophosphamide (Drug)
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: etoposide (Drug)
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: tomotherapy (Radiation)
Level 4: 1500cGy limited dose to liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 4: 1500cGy limited dose to liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 4: 1500cGy limited dose to liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 4: 1500cGy limited dose to liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 4: 1500cGy limited dose to liver, brain 1200cGy
150cGy BID Day 1-5. Total dose 1500Gy.
干预措施: tomotherapy (Radiation)
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
160cGy BID Day 1-5. Total dose 1600Gy.
干预措施: cyclophosphamide (Drug)
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
160cGy BID Day 1-5. Total dose 1600Gy.
干预措施: etoposide (Drug)
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
160cGy BID Day 1-5. Total dose 1600Gy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
160cGy BID Day 1-5. Total dose 1600Gy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
160cGy BID Day 1-5. Total dose 1600Gy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
160cGy BID Day 1-5. Total dose 1600Gy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
160cGy BID Day 1-5. Total dose 1600Gy.
干预措施: tomotherapy (Radiation)
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
170cGy BID Day 1-5. Total dose 1700Gy.
干预措施: cyclophosphamide (Drug)
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
170cGy BID Day 1-5. Total dose 1700Gy.
干预措施: etoposide (Drug)
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
170cGy BID Day 1-5. Total dose 1700Gy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
170cGy BID Day 1-5. Total dose 1700Gy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
170cGy BID Day 1-5. Total dose 1700Gy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
170cGy BID Day 1-5. Total dose 1700Gy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
170cGy BID Day 1-5. Total dose 1700Gy.
干预措施: tomotherapy (Radiation)
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
180cGy BID Day 1-5. Total dose 1800Gy.
干预措施: cyclophosphamide (Drug)
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
180cGy BID Day 1-5. Total dose 1800Gy.
干预措施: etoposide (Drug)
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
180cGy BID Day 1-5. Total dose 1800Gy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
180cGy BID Day 1-5. Total dose 1800Gy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
190cGy BID Day 1-5. Total dose 1900Gy.
干预措施: tomotherapy (Radiation)
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
180cGy BID Day 1-5. Total dose 1800Gy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
180cGy BID Day 1-5. Total dose 1800Gy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
180cGy BID Day 1-5. Total dose 1800Gy.
干预措施: tomotherapy (Radiation)
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
190cGy BID Day 1-5. Total dose 1900Gy.
干预措施: cyclophosphamide (Drug)
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
190cGy BID Day 1-5. Total dose 1900Gy.
干预措施: etoposide (Drug)
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
190cGy BID Day 1-5. Total dose 1900Gy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
190cGy BID Day 1-5. Total dose 1900Gy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
190cGy BID Day 1-5. Total dose 1900Gy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
190cGy BID Day 1-5. Total dose 1900Gy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
200cGy BID Day 1-5. Total dose 2000Gy.
干预措施: cyclophosphamide (Drug)
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
200cGy BID Day 1-5. Total dose 2000Gy.
干预措施: etoposide (Drug)
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
200cGy BID Day 1-5. Total dose 2000Gy.
干预措施: allogeneic bone marrow transplantation (Procedure)
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
200cGy BID Day 1-5. Total dose 2000Gy.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
200cGy BID Day 1-5. Total dose 2000Gy.
干预措施: peripheral blood stem cell transplantation (Procedure)
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
200cGy BID Day 1-5. Total dose 2000Gy.
干预措施: intensity-modulated radiation therapy (Radiation)
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
200cGy BID Day 1-5. Total dose 2000Gy.
干预措施: tomotherapy (Radiation)
结局指标
主要结局
Maximum Tolerated Dose of Intensity-modulated Radiotherapy (Phase I)
时间窗: 30 days post transplant
Toxicities will be recorded using two distinct grading systems: the modified Bearman scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 3.0 scale.
次要结局
未报告次要终点