Phase I/II Evaluation of Safety and Activity of Mylotarg Plus Melphalan and Fludarabine as Preparative Therapy for Older or Medically Infirm Patients Undergoing Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
研究概览
简要总结
The goal of this clinical research study is to find the highest safe dose of Mylotarg that can be combined with chemotherapy in patients receiving allogeneic bone marrow transplantation. Researchers will study the effects of this treatment combination on patients with high-risk acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome.
Primary Objective:
- To determine the safety and maximum tolerated dose of Mylotarg as part of a reduced-intensity preparative regimen patients undergoing related, mismatched-related or matched unrelated donor transplantation.
Secondary Objectives:
- To evaluate response rates, engraftment kinetics and degree of chimerism achievable with this strategy.
- To evaluate the incidence and severity of GVHD in this population
- To evaluate disease-free and overall survival and relapse rates.
详细描述
Before treatment starts, patients will have a complete physical exam, including blood and urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone marrow biopsy. Women who are able to have children will have a pregnancy test.
In this study, patients will receive Mylotarg twelve days before the transplant. The first patients will receive Mylotarg at the lowest dose level. As the study continues, the dose levels will be increased as long as no severe side effects occur. Mylotarg may be given in the outpatient Ambulatory Treatment Center (ATC). Patients will be monitored in the ATC for eight hours on the day of infusion. For the next 5 days, patients will be evaluated in the Clinic on a daily basis or as per physician orders. One week before the transplant, all patients will be admitted to the hospital and will continue their treatment as inpatients. Patients experiencing side effects from their leukemia or leukemia treatment may need to be hospitalized earlier.
On the 1st day of hospitalization, patients will receive fluids by vein. On the 5th, 4th, 3rd and 2nd day before the transplant, patients will receive Fludarabine, by vein. Melphalan will be given by vein on the 2nd day before transplant. Patients receiving five out of six antigen matched or unrelated bone marrow will also receive antithymocyte globulin, by vein, on the 3rd, 2nd and 1st day before transplant.
On the 7th day, healthy blood stem cells or bone marrow from the donor will be given through the central catheter. Some donor bone marrow or stem cells may be saved for future therapies.
Patients will also receive several other medications to help the treatment work and to help prevent infections while their immune system is weak. Tacrolimus and methotrexate will be given to prevent graft-versus-host disease (GVHD). GVHD occurs when the donor's immune cells fight the patient's body. The Tacrolimus will be started on the day before the transplant and will continue for up to six months. Tacrolimus is given by vein at first and then by mouth when patients are able to eat. Methotrexate is given by vein on days 1, 3, 6 and possibly on day 11 after the transplant.
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
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 12-75 years of age
- •Patients are eligible if deemed ineligible for conventional high dose chemotherapy programs because of concurrent medical conditions. Patients with refractory AML are always eligible if ejection fraction > 35, FEV1, FVC, or DLCO > 40%, abnormal LFT's.
- •Patients must have recovered from previous Grade III-IV toxicity due to prior anti-neoplastic therapy (except alopecia).
- •Patients with the following disease categories will be eligible:
- •AML with induction failure, relapse or 2nd remission
- •MDS with IPI INT-2 or High-risk disease (Appendix 4) or CMML
- •CML in accelerated phase or blast crisis
- •Interferon or STI resistant CML not eligible for conventional stem cell transplant
- •Patients receiving prior BMT are eligible. If myeloablative chemoradiotherapy was used in the prior transplant patients must be >90 days from transplant. If non-myeloablative therapy was used patients must be >30 days post-transplant.
- •Leukemia cells must express cell surface CD33 evaluated by flow cytometry in > 20% of leukemia cells.
- •Patients must have an HLA-compatible related donor (6/6 or 5/6 HLA-match) capable of donating bone marrow or G-CSF stimulated peripheral blood stem cells using aphereses techniques or a 6/6 HLA matched unrelated bone marrow donor (serologic matching for Class I, molecular matching for DR?1).
- •Patients must have a ECOG PS<2 (Appendix 6), Cr<2.0, bilirubin <2, and (SGPT) <3x normal
- •Patients must have an estimated life expectancy > 3 months
- •Patient and donor must sign informed consent. Unrelated donors will be consented according to the National Donor Marrow Registry policy
排除标准
- •uncontrolled active infection
- •HIV disease
- •pregnancy and nursing
- •active, uncontrolled CNS leukemia
研究组 & 干预措施
Chemotherapy + ATG + Stem Cell Infusion
干预措施: Mylotarg (Drug)
Chemotherapy + ATG + Stem Cell Infusion
干预措施: Fludarabine (Drug)
Chemotherapy + ATG + Stem Cell Infusion
干预措施: Melphalan (Drug)
Chemotherapy + ATG + Stem Cell Infusion
干预措施: Anti-thymocyte globulin (Drug)
Chemotherapy + ATG + Stem Cell Infusion
干预措施: Stem cell transplant (Procedure)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
时间窗: Followed in outpatient clinic from day -12 (prior to transplant) thru day -6 with each dose level
次要结局
- Patient Response(Continously over first 30 days)