NCT01596699终止2 期
A Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Related Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
The purpose of this study is to find out what effects, good and/or bad, the addition of clofarabine, a new chemotherapy agent, to a standard busulfan and fludarabine conditioning treatment has. The study will also look at what causes some people to have high drug levels of these medications in their body compared to other people that may have low drug levels even if they all receive the same dose of medication.
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
- 3 Months 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥ 3 months and ≤30 years of age.
- •Stratum A: Non-Malignant Diseases, including:
- •Bone Marrow Failure Syndromes
- •Hemoglobinopathies or transfusion-dependent red blood cell (RBC) defects
- •Congenital Immunodeficiencies
- •Metabolic Diseases known to be treatable with Hematopoietic cell transplantation (HCT) (e.g. Hurler's)
- •Other Bone Marrow Stem Cell Defects (e.g. Osteopetrosis)
- •Severe Immune Dysregulation / Autoimmune Syndromes with at least transient prior response to immunosuppressive therapy
- •Stratum B: Myeloid Malignancies, including:
- •acute myeloid leukemia (AML), in greater than first clinical remission, or in CR1 but with detectable disease (≥0.1% Blasts by minimal residual disease (MRD) or Flow, or Positive Cytogenetics), or in CR1 but with a matched sibling Umbilical cord blood (UCB) donor.
- •Myelodysplastic syndromes (MDS)
- •Juvenile myelomonocytic leukemia (JMML)
- •Chronic myeloid leukemia (CML), with detectable disease by polymerase chain reaction (PCR)
- •Patients must have a suitable donor based on the University of California, San Francisco (UCSF) Pediatric Bone Marrow Transplant (BMT) standard operating procedures (SOP). 10/10 (HLA-A, -B, -C, -DR, -DQ) matching will be done for related and adult unrelated donors; 8/8 (HLA-A, -B, -C, -DR) for umbilical cord blood donors. Patients with non-malignant diseases will generally be eligible only if they have a mismatched donor, or an accepted clinical reason to be considered high-risk for rejection.
- •Liver transaminases (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)) and Direct Bilirubin less than twice the upper limit of normal within 2 weeks of admission.
- •Cardiac Shortening Fraction ≥27% within 4 weeks of admission.
- •Creatinine clearance by Schwartz formula, glomerular filtration rate (GFR) or 24 hr urine collection ≥50 cc/min/1.73 m2, within 4 weeks of admission.
- •Pulmonary diffusion capacity ≥50% of predicted corrected for anemia/lung volume within 4 weeks of admission. If unable to do Pulmonary function testing(PFTs), then no active lung disease by chest x-ray (CXR) and/or oxygen (O2) Saturation ≥90% on room air.
排除标准
- •Fanconi Anemia
- •Dyskeratosis Congenita
- •A known syndrome with increased sensitivity to radiation or alkylating agents
- •Severe Combined Immunodeficiency Disease eligible for a non-myeloablative HCT Trial
- •A mismatched donor for whom ex vivo T-cell depletion of the donor stem cells is planned
研究组 & 干预措施
Patients with Non-Malignancies
Experimental
干预措施: Busulfan (Drug)
Patients with Myeloid Malignancies
Experimental
干预措施: Busulfan (Drug)
Patients with Myeloid Malignancies
Experimental
干预措施: Fludarabine (Drug)
Patients with Myeloid Malignancies
Experimental
干预措施: Clofarabine (Drug)
Patients with Non-Malignancies
Experimental
干预措施: Alemtuzumab (Drug)
Patients with Non-Malignancies
Experimental
干预措施: Fludarabine (Drug)
Patients with Non-Malignancies
Experimental
干预措施: Clofarabine (Drug)
结局指标
主要结局
Number of Participants With Treatment-Related Adverse Events as a Measure of Safety and Tolerability
时间窗: Up to 5 years on average
Severe Toxicity will be defined as death or Grade IV by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 pulmonary or hepatic failure (including moderate veno-occlusive disease(VOD) related to the transplant conditioning regimen within 100 days post-HCT. VOD will be defined by standard criteria. Patients must have Bilirubin \>2.0 plus Hepatomegaly and/or Right upper quadrant (RUQ) pain plus Weight gain \>5%.
次要结局
- Serum Concentrations and Potential for Drug-drug Interaction of Fludarabine and Clofarabine(Pharmacokinetics (PK) blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant.)
- Engraftment Rate of Patients With Non-malignant Diseases (Stratum A)(Participants will have engraftment blood studies starting approximately Day 30 post hematopoietic stem cell transplant and then monthly until stable. Average study participation is approximately 5 years.)
- Mixed-donor Chimerism Rate of Patients With High-risk Myeloid Malignancies (Stratum B)(Participants will have peripheral blood chimerism assessed at Day 100 post hematopoietic stem cell transplant and then monthly until stable.)
研究者
研究点 (1)
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