A Phase I/IIa, Open-label, Non-randomized, Study of ASC-101 in Patients With Hematologic Malignancies or Myelodysplastic Syndrome (MDS) Who Are Candidates for Dual-cord Umbilical Cord Blood Transplantation (UCBT)
试验速览
- 阶段
- 1 期
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Safety and tolerability in patients who receive ASC-101-treated dual-cord UCBT
研究概览
简要总结
The goal of this clinical research study is to learn if it is safe and feasible to transplant patients with one of two units of cord blood that has been changed in the laboratory before it is given. Only patients with leukemia, lymphoma or myelodysplastic syndrome will be allowed on this study. The secondary goal is to obtain the preliminary efficacy outcome. Researchers also want to learn if using cord blood that has been changed can help to control the disease.
One cord blood unit will not be changed before it is administered to you. The cord blood unit that will be altered will be changed to use sugar that is found in small amounts in blood cells. It plays a role in telling transplanted cells where they should go in the body. Adding more sugars to the cord blood cells in the laboratory helps the cord blood cells find their way to the bone marrow faster. This process is called fucosylation.
"Conditioning" is the chemo and other medicines and will be given to patients to prepare to receive cord blood transplant cells. This prevents immune system from rejecting the cells. Conditioning will be started before the transplant.
ATG is a protein that removes immune cells that cause damage to the body.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die. This chemotherapy is also designed to block your body's ability to reject the donor's bone marrow cells.
Melphalan and busulfan are designed to bind to the DNA of cells, which may cause cancer cells to die.
MMF and tacrolimus are designed to block the donor cells from growing and spreading in a way that could cause graft versus host disease (GVHD -- a condition in which transplanted tissue attacks the recipient's body). This may help to prevent GVHD.
Rituximab is designed to attach to cancer cells, which may cause them to die.
A Phase I study for treatment of patients (N=25) with hematologic malignancies and MDS who are candidates for dual-cord UCBT is ongoing at M.D. Anderson Cancer Center under an Investigator-initiated IND Application, E.J. Shpall, MD, PI. Since August, 2012, Preliminary results indicate that ASC-101 UCBT is well-tolerated and no ASC-101 related untoward adverse events have been observed. To date, the median time to neutrophil engraftment (N=9) is 15 days, and the median time to platelet engraftment (N=9) is 33 days. The trial remains ongoing.
详细描述
Central Venous Catheter Placement:
You will first have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.
The chemotherapy, some of the other drugs in this study, and the cord blood transplant will be given by vein through your CVC. Blood samples will also be drawn through your CVC. The CVC will remain in your body for about 2-5 months.
Study Plans:
If you agree to take part in this study, your doctor will choose one of the following 2 study plans based on the disease and your age and medical history.
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
- 1 Year 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females: 1 to 80 years of age
- •Patients with AML, ALL, CML, CLL, MDS, NHL or HD:
- •Patients with AML: first complete remission (CR1) with high-risk for relapse (e.g., high-risk cytogenetics, molecular mutation [FLT3, MEK, MLL, other] and/or persistent minimal residual disease by evidence of flow cytometry < 20% blasts in marrow), secondary leukemia from prior chemotherapy and/or arising from MDS, Langerhan's cell histiocytosis, second or third complete remission (CR2 or CR3) Patients with ALL: CR1 with Philadelphia chromosome or translocation 4;11, hypodiploidy, and/or persistent minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy, CR2 or CR3 Patients with CML: second chronic phase after failure or intolerant of tyrosine kinase inhibitors, or accelerated phase Patients with MDS: IPPS INT-1 or higher and failed prior therapy Patients with NHL: CR2 or CR3 following response to prior therapy, or relapse, including relapse following autologous HSCT Patients with HD: CR2 or CR3 following response to prior therapy, or relapse, including relapse following autologous HSCT
- •KPS of 80 or ECOG < 3 (age 12 years) or Lansky Play Performance Score of > 60% (age < 12 years). Eligibility for pediatric patients will be determined in conjunction with an Institutional pediatrician.
- •Laboratory data:
- •ALT/AST < 2.0 times the upper limit of normal (ULN) Total bilirubin < 2.0 times ULN Creatinine < 1.6 mg/dL
- •Left ventricular ejection fraction (LVEF) ≥ 40%
- •Pulmonary function test (PFT) demonstrating diffusion capacity of lung for carbon monoxide (DLCO) ≥ 50% of predicted. For children < 7 years of age who are unable to perform PFT, oxygen saturation > 92% on room air by pulse oximetry allowed.
- •Patients must have 2 UCB unit available, each matched with the patient at 4, 5, or 6/6 collect all 10 HLA class I (serological) and II (molecular) antigens. Each UCB unit must contain a minimum dose of 1.5 x107 (red blood cell depleted) TNC per kg per cord pre-thaw. Information on HLA-C and DQ loci will be collected for future analysis.
- •Have a back-up cell source identified in case of engraftment failure. The source can be autologous, allogeneic (related or unrelated).
- •Negative beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to use an effective contraceptive measure while on study
- •Patient, or guardian, ability to provide written informed consent
排除标准
- •Prior allogeneic transplant
- •Patients with 6/6 HLA-matched sibling donors, 10/10 HLA-matched unrelated donors (MUD), or untimely availability of 10/10 HLA-MUD relative to need to take patient to transplant
- •Active, uncontrolled infection, decompensated congestive heart failure or pulmonary insufficiency requiring oxygen supplementation
- •Active central nervous system (CNS) disease in patients with a history of CNS malignancy
- •Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence with study requirements
- •Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV) or rapid plasma regain (RPR) test for syphilis
- •Pregnant or breast-feeding
- •Treatment with any investigational product within 28 days prior to Screening
研究组 & 干预措施
Fludarabine, Clofarabine, Busulfan, ATG, TBI (Myeloablative)
Fludarabine, Clofarabine, Busulfan, Anti-thymocyte Globulin (ATG), Total Body Irradiation (TBI) (Myeloablative) Day Treatment
- Day0 Admit, IV hydration, rituximab 375 mg/m2 (B cell malignancy)
- Day 1 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000
- Day2 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000
- Day3 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000
- Day4 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000, rabbit ATG 1.25 mg/kg
- Day5 Low-dose TBI 2 Gy in AM, rabbit ATG 1.75 mg/kg
- Day6 Rest
- Day7 Rest
- Day8 Cord blood infusions
干预措施: Fludarabine, Clofarabine, Busulfan, ATG, TBI (Myeloablative) (Drug)
Fludarabine, Melphalan, ATG (Reduced Intensity)
Day Treatment
- Day0 Admit, hydration
- Day1 Fludarabine 40 mg/m2 IV
- Day2 Fludarabine 40 mg/m2 IV, rabbit ATG 1.25 mg/kg
- Day3 Fludarabine 40 mg/m2 IV, rabbit ATG 1.75 mg/kg
- Day4 Fludarabine 40 mg/m2 IV and Melphalan 140 mg/m2 IV
- Day5 Rest Day6 Cord blood infusions
干预措施: Fludarabine, Melphalan, ATG (Reduced Intensity) (Drug)
结局指标
主要结局
Safety and tolerability in patients who receive ASC-101-treated dual-cord UCBT
时间窗: 42 days
All safety endpoints will be summarized using descriptive statistics; no inferential testing is planned. For chimerism, graphic presentations of changes from baseline will be provided.
次要结局
- Preliminary efficacy of ASC-101-treated dual-cord UCBT, as assessed by the rate of reconstitution of neutrophils and platelets as compared to historical controls receiving an unmanipulated dual-cord UCBT(180 days)