A Phase II Trial of Inhibition of CD26 Peptidase Using Sitagliptin to Enhance Engraftment After Umbilical Cord Blood Transplantation for Adults With Hematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Cumulative Incidence of Patients With Engraftment by Day +30 Following Transplant
研究概览
简要总结
The main purpose of this trial is to study whether the drug sitagliptin can be given safely to patients undergoing umbilical cord blood transplantation to speed up engraftment (recovery of blood counts after transplant).
详细描述
Umbilical cord blood (UCB) is increasingly used as a source of stem cells for patients with blood cancers who need an allogeneic stem cell transplant (a transplant with stem cells from another person) but who have no suitably matched donors. The advantages of UCB are that (1) it is associated with less risk of transmitting an infection from a donor, (2) it can be more safely given even if not completely matched compared to bone marrow or blood stem cells, and (3) it is much more quickly available than unrelated donor bone marrow or blood stem cells. While more commonly used for transplantation in children, UCB is increasingly being used in adults. However, because they are larger than children, the relatively smaller stem cell dose in UCB is major limitation for transplantation in adults, and engraftment can be delayed. This study is investigating whether the drug sitagliptin can be used to increase and speed up engraftment in adults receiving UCB transplantation, overcoming the limitation of small stem cell doses associated with umbilical cord blood.
Sitagliptin is a drug given in tablet form that has been recently approved by the Food and Drug Administration (FDA) for the treatment of certain patients with diabetes mellitus (a disease that results in high blood sugar). Sitagliptin has been given to both normal healthy volunteers and diabetic patients and has been found to be safe and well-tolerated. The drug improves control of blood sugar in diabetics by inhibiting an enzyme called "CD26/DPP-IV." Recent studies at Indiana University (and other centers) have shown that this same enzyme plays an important role in the way transplanted stem cells find their way to the bone marrow and engraft. Transplant studies in mice have found that inhibiting CD26/DPP-IV significantly increases the engraftment of stem cells. Based on these studies, it is believed that drugs that inhibit CD26/DPP-IV, such as sitagliptin, may also increase engraftment in patients who receive clinical stem cell transplants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have one of the following disease types with disease-specific features as outlined in the protocol:
- •Acute myeloid leukemia (AML)
- •Acute lymphoblastic leukemia (ALL)
- •Myelodysplasia
- •Chronic myelogenous leukemia
- •Patients with aggressive non-Hodgkin's lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma
- •Hodgkin's lymphoma
- •Relapsed Multiple Myeloma
- •At least 35 days following start of preceding leukemia induction cytotoxic chemotherapy
- •Patient age 18-55 years
- •Karnofsky Performance status ≥ 70%
- •No availability of a consenting HLA-matched related donor who is either matched fully matched or mismatched at only one locus of HLA-A, -B, and DRB
- •No availability of a readily available HLA-matched volunteer unrelated donor (8 of 8 allele match at HLA-A, -B, -C and -DRB1). Patients with unstable disease who are in danger of significant disease progression while waiting to procure volunteer donor cells will be eligible to be treated on this protocol, even if a matched donor is available.
- •Patients must have a matched or partially matched UCB unit with greater than 1.8 x10-7 nucleated cells/kg of recipient weight at the time of cryopreservation.
- •No current uncontrolled bacterial, viral or fungal infection (defined as currently taking medication and progression of clinical symptoms).
- •No HIV disease. Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies.
- •Non pregnant and non-nursing. Treatment under this protocol would expose a fetus to significant risks.
- •Required baseline laboratory values as defined in the protocol
排除标准
- •Symptomatic uncontrolled coronary artery disease or congestive heart failure.
- •Severe hypoxemia with room air PaO2 less than 70, supplemental oxygen dependence, or DLCO less than 50 percent predicted
- •Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy
- •Prior allogeneic or autologous hematopoietic stem cell transplant in the last 6 months
研究组 & 干预措施
Sitagliptin once per day
600 mg sitagliptin once per day orally starting on Day -1 for a total of 4 doses
干预措施: Sitagliptin (Drug)
Sitagliptin twice per day
600 mg sitagliptin twice per day orally starting on Day -1 for a total of 8 doses
干预措施: Sitagliptin (Drug)
Sitagliptin three times per day
600 mg sitagliptin three times per day orally starting on Day -1 for a total of 12 doses
干预措施: Sitagliptin (Drug)
结局指标
主要结局
Cumulative Incidence of Patients With Engraftment by Day +30 Following Transplant
时间窗: Transplant (Day 0) through Day +30
Evaluate the efficacy of CD26/DPP-IV inhibition in increasing the cumulative incidence of adult patients with hematological malignancies engrafting by day +30 following transplantation of UCB by 30 percent. The cumulative incidence of patients achieving this will be reported. The value of the estimate will be from bootstrapping 1000 samples with replacement of the data and the 95% confidence interval will be calculated using the percentile method.
次要结局
- Time to Neutrophil Engraftment(Transplant (Day 0) up to 1 year)
- Time to Platelet Engraftment(Transplant (Day 0) up to 1 year)
- Treatment Related Adverse Events Grade 3 or Higher for Non-hematological Toxicity(Transplant (Day 0) up to 3 years)