Phase I-II Single Cycle Melphalan/Total Marrow Irradiation (TMI) and Autologous Stem Cell Transplantation (ASCT) Followed by Maintenance in Patients With High-Risk Myeloma and/or Poor Response to Induction Therapy Within 12 Months of Diagnosis
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of mel/TMI (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of melphalan and total marrow irradiation and how well they work with autologous stem cell transplantation in treating patients with high-risk multiple myeloma. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Total marrow irradiation is a type of radiation therapy and a form of total body irradiation that may deliver focused radiation to the major marrow sites where cancer cells reside. Giving chemotherapy and total-body irradiation before a peripheral autologous blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then 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 assess the safety and determine the maximum tolerated dose (MTD) of melphalan and fractionated total marrow irradiation (TMI) as conditioning regimen for autologous stem cell transplantation (ASCT) in patients with high-risk or treatment-insensitive multiple myeloma (MM). (Phase I) II. Evaluate the safety of the regimen at each dose level by assessing adverse events: type, frequency, severity, attribution, time course, duration.
III. Evaluate the safety of the regimen at each dose level by assessing complication including: infection, delayed engraftment and secondary malignancy.
IV. To assess complete response (CR) and minimal residual disease (MRD) rates at 100 days post ASCT in a phase II expanded cohort of patients treated at the MTD. (Phase II)
SECONDARY OBJECTIVES:
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with will be eligible if they are either in partial response, or have stable disease after no more than two attempts of induction therapy
- •Patients with high-risk cytogenetics, t(4:14); t(14;16), t(14:20), deletion p17, gain in 1q, are eligible
- •Patients with plasma cell leukemia in >= partial remission are eligible
- •Patients with non-quantifiable monoclonal proteins are eligible provided they meet other criteria for multiple myeloma and they have evaluable or measurable disease by other (radiographic, magnetic resonance imaging [MRI], computed tomography [CT], lytic measurable lesion on x-ray,) means
- •Karnofsky performance status (KPS) >= 70%
- •Less than 12 months since diagnosis
- •No contraindication to the collection of a minimum of 4 x 10^6 CD34+ cells/kg by apheresis
- •Bilirubin =< 1.5 mg/dl
- •Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x upper limits of normal
- •Creatinine of measured or calculated creatinine clearance of >= 50 cc/min
- •Absolute neutrophil count of > 1000/ul
- •Platelet count of > 100,000/ul
- •Cardiac ejection fraction >= 50% by multi-gated acquisition (MUGA) scan and/or by echocardiogram
- •Forced expiratory volume in 1 second (FEV1) > 60% and diffusion capacity of the lung for carbon monoxide (DLCO) > 50% of predicted lower limit
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately; patients must be fully aware of the teratogenic potential of immunomodulatory drugs (ImIDs) and agree to fully comply with the mandated guidelines regarding contraception as stated in the informed consent and the patient warning document attached to the consent form; women of childbearing potential must have a negative pregnancy test performed within 24 hours prior to beginning thalidomide, except for woman who have been postmenopausal for at least 2 years, or underwent hysterectomy; use of effective means of contraceptive should be started at least 2 weeks prior to initiating lenalidomide
- •All subjects must have the ability to understand and the willingness to sign a written informed consent; they are to give voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- •Patients should have finished their prior systemic therapy or radiation therapy, at least 3 weeks before cyclophosphamide or granulocyte colony-stimulating factor (G-CSF)/plerixafor mobilization, and should have finished dexamethasone at least 7 days prior to Plerixafor priming; administration of bisphosphonates needs to be completed at least 2 weeks before cyclophosphamide priming; bisphosphonates can be resumed or started after day 30
排除标准
- •Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low-risk prostate cancer after curative therapy
- •Known hypersensitivity to filgrastim or to Escherichia coli (E. coli) derived proteins
- •Inability to lie supine in a full body cast for approximately 30 minutes, the anticipated duration of each treatment session
- •Previous radiation therapy to more than 20% of bone marrow containing areas, or to any area exceeding 2000 cGy, is an exclusion
- •Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded
- •No other medical, or psychosocial problems, which in the opinion of the primary physician or principal investigator would place the patient at unacceptably high risk from this treatment regimen
研究组 & 干预措施
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Cyclophosphamide (Drug)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Filgrastim (Biological)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Lenalidomide (Drug)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: pheresis (Procedure)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Melphalan (Drug)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Palifermin (Biological)
Treatment (mel/TMI, ASCT)
MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10.
CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.
MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.
干预措施: Total Marrow Irradiation (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of mel/TMI (Phase I)
时间窗: Up to 3 years
Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.
Complete Response (CR) post-Autologous Stem Cell Transplantation (ASCT) (Phase II)
时间窗: Up to 3 years
Will be summarized both by pooling across dose levels and by dose level.
次要结局
未报告次要终点