Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Participants With Multiple Myeloma or Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Non-relapse Mortality (NRM) at Day 100
研究概览
简要总结
This phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and cyclophosphamide in treating participants with multiple myeloma or myelofibrosis. Drugs used in chemotherapy, such as busulfan, fludarabine, and cyclophosphamide, 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. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving busulfan and fludarabine before and cyclophosphamide after donor stem cell may work better in treating participants with multiple myeloma or myelofibrosis.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate non-relapse mortality (NRM) up to day +100.
SECONDARY OBJECTIVES:
I. To evaluate non-relapse mortality (NRM) up to day +365. II. To evaluate the incidence of acute graft versus host disease (GVHD) and chronic GVHD up to day +365 post-transplant.
III. To evaluate the overall survival and disease free survival up to 1 year. IV. To evaluate clinical response and molecular response (complete response and partial response) up to 1 year.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Participants must have one of the following diagnoses of multiple myeloma (MM) or primary/secondary myelofibrosis (MF)
- •Participants must have histologically documented multiple myeloma (MM)
- •Participants in early relapse (less than 24 months from initiation of systemic anti-myeloma therapy which may include single or planned tandem autologous transplant) after primary therapy that included and autologous HSCT; OR
- •Later stage; OR
- •High risk factors defined by the presence of any one of the following detected at any time prior to enrollment: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1 (1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high risk criteria based on commercially available gene expression profiling; OR
- •Extramedullary disease, plasma cell leukemia or high lactate dehydrogenase (LDH)
- •Participants must have histologically documented myelofibrosis (MF)
- •Participants with Dynamic International Prognostic Scoring System (DIPSS) plus intermediate stage 2 or higher risk MF; OR
- •Subset of intermediate stage 1 participants; defined by:
- •Poor-risk molecular profile (triple negative: JAK2, CALR, MPL); OR
- •Presence of any of the following mutations: ASXL1, SRSF2, EZH2, IDH1/2; OR
- •Severe thrombocytopenia, severe anemia, high peripheral blood blasts percentage; OR
- •Unfavorable cytogenetic abnormalities (rearrangements of chromosome 5 or 7 or >= 3 abnormalities
- •Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
- •DONOR: A related donor - fully matched
- •DONOR: A related donor - haploidentical
- •DONOR: An unrelated donor - fully matched
- •DONOR: An unrelated donor -9/10 matched
排除标准
- •Cardiac-left ventricular ejection fraction < 40%, symptomatic coronary artery disease, or uncontrolled arrhythmias
- •Pulmonary-forced expiratory volume at one second (FEV1) or diffusion capacity of lung for carbon dioxide (DLCO) < 40% or history of chronic use of supplemental oxygen. Temporary use of supplemental oxygen at the time of screening or registration is allowed if the investigator feels that the underlying cause of requiring oxygen is reversible by the time treatment begins.
- •Renal-calculated or measured glomerular filtration rate (GFR) < 30 ml/min, dialysis-dependent, or history of renal transplant
- •Hepatic-bilirubin > 2 X upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) > 2.5 X ULN or cirrhosis
- •Participants with active or uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
- •Pregnant women, nursing mothers or women of child-bearing potential who are unwilling to use medically accepted methods of contraception
- •Male and female subjects not willing to agree to medically accepted methods of contraception
研究组 & 干预措施
Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
干预措施: Busulfan (Drug)
Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
干预措施: Cyclophosphamide (Drug)
Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
干预措施: Fludarabine (Drug)
Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
干预措施: Hematopoietic Cell Transplantation (Procedure)
Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Non-relapse Mortality (NRM) at Day 100
时间窗: Up to day 100
NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
次要结局
- Non-relapse Mortality (NRM) at Day 365(Up to day 365)
- Incidence of Chronic GVHD(Up to day 365)
- Incidence of Acute Graft Versus Host Disease (GVHD)(Up to day 365)
- Number of Participants With Different Clinical Responses(Up to 1 year)
- Overall Survival at One Year(Up to 1 year)
- Disease Free Survival at One Year(Up to 1 year)
- Number of Participants With Minimal Residual Disease (MRD) Response(Up to 1 year)