A Phase I, Multicenter, Dose-Escalation Trial Evaluating Maximum-Tolerated Dose of Single and Repeated Administration of Allogeneic MultiStem® in Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplasia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Healios K.K.
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- maximum tolerated dose
研究概览
简要总结
The purpose of this study is to determine if MultiStem® can safely be given to patients with acute leukemia, chronic myeloid leukemia, or myelodysplasia after they have received hematopoietic stem cell transplantation.
详细描述
Graft-vs.-Host Disease (GVHD) is one of the major limitations of allogeneic hematopoietic stem cell transplants (HSCT). This complication is major cause of morbidity and mortality and is thought to be initiated by activation of donor T-cells through recognition of "foreign" cells resident in the transplant recipient. Acute GVHD is associated with damage to the liver, skin, gastrointestinal tract and mucosa. Moderate to severe GVHD Grades II-IV occurs in 30-50% of matched related HSCTs and 50-70% of unrelated donor recipients. Severe GHVD requires intense immunosuppression involving steroids and additional agents to get it under control, and patients may develop severe infections as a result of such immunosuppression. An agent or cell therapy that could reduce the incidence and/or severity of GVHD without increasing relapse or infectious risk in HSCT patients would provide substantial benefits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of either sex aged 18-65 years of age
- •Diagnosis of acute myeloid or lymphoblastic leukemia (second or subsequent remission, if not in remission, then <20% bone marrow blasts), chronic myelogenous leukemia resistant to or intolerant of tyrosine kinase inhibitor therapy (accelerated phase, first chronic phase with TKI resistance, or second chronic phase), or myelodysplastic syndrome (intermediate/high or high risk by International Prognostic Scoring System (IPSS), lower risk by IPSS with patient having progressed after prior therapy. Complete remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment and <5% blasts in the marrow within 28 days of enrollment.
- •Life expectancy of at least 100 days
- •Patients scheduled for allogeneic bone marrow transplant or peripheral blood stem cell transplant (PBST) procedure
- •Family-related or unrelated donors
- •HLA matching should either be matched related or matched unrelated donors, 6/6 match or 5/6 single allelic mismatch, with provision that the DRB1 is molecularly matched
- •Performance status (ECOG ≤2)
- •Signed informed consent
排除标准
- •Active infection
- •Known allergies to bovine or porcine products
- •Renal function: Serum creatinine >2 mg/dL or creatinine clearance ≤50 mL/min
- •Hepatic function: Screening ALT or AST ≥3x than the upper limit of normal for the laboratory OR total bilirubin ≥2.0 mg/dL (Exception: acceptable if patient is identified with pre-existing condition e.g., Gilbert's disease that will contribute to baseline elevations of bilirubin)
- •Pulmonary function: FEV1, FVC, DLCO ≤50% predicted
- •Cardiac function: left ventricular ejection fraction ≤50%
- •Patient received an investigational agent within 30 days prior to transplant
- •The patient is pregnant, has a positive serum BhCG, or is lactating
- •Patient on corticosteroids at a dose >0.25 mg/kg/day
- •Planned non-myeloablative transplant
- •Planned cord blood transplant
- •Prior allogeneic myeloablative HSCT
- •HIV seropositive, HTLV seropositive, hepatitis B or C seropositive, varicella virus active infection, or syphilis active infection
- •Other serious medical or psychiatric illness that, in the investigator's opinion, would not permit the patient to be managed according to the protocol
研究组 & 干预措施
Single dose Arm
There will be six cohorts of three patients each. Three escalating doses of MultiStem will be evaluated.
干预措施: MultiStem® (Biological)
Repeat Dose Arm
There will be six cohorts of three patients each. Four dosing regimens will be evaluated,varying doses at three times weekly or five times weekly.
干预措施: MultiStem® (Biological)
结局指标
主要结局
maximum tolerated dose
时间窗: 30 days
次要结局
- incidence of grade III/IV GVHD(100 days)