A Phase II Study of Thiotepa Added to Fludarabine and Melphalan as the Preparative Regime for Alternative Donor Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Percentage of Patients With Disease Free Survival
研究概览
简要总结
In the United States, thiotepa has been utilized in reduced intensity conditioning regimens for alternative donor courses (double umbilical cord blood transplant (dUCBT) and haplo-identical transplants).
The hypothesis is that thiotepa at a dose of 10mg/kg, in combination with melphalan (100mg/m2) and fludarabine (160mg/m2) as a reduced intensity conditioning regimen for alternative donor transplant is safe and effective in patients with hematologic malignancies.
Given that this regimen has been investigated extensively, and the current study proposes to confirm those previous observations with a small modification (melphalan dose reduction due to previous mucositis rates with higher doses), this will be a phase II study designed to measure disease-free-survival.
详细描述
Primary Objective:
To assess the effectiveness of Thiotepa, Fludarabine, and Melphalan in alternative donor transplants as measured by leukemia free survival.
Secondary Objective:
To assess the 1- year OS, Relapse, TRM, aGVHD and cGVHD rates and the rates of neutrophil and platelet engraftment.
Study Design This is a Phase II study of Thiotepa, Fludarabine, and Melphalan in alternative donor transplants.
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
- 1 Year 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with the following hematologic malignancies:
- •Acute myelogenous leukemia (AML): High-risk AML including:
- •Antecedent hematological disease (e.g., myelodysplasia (MDS))
- •Treatment-related leukemia
- •Complete Remission (CR1) with poor-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, complex cytogenetics)
- •Second complete remission (CR2) or third complete remission (CR3)
- •Induction failure or 1st relapse with ≤ 10% blasts in the marrow
- •Acute lymphoblastic leukemia (ALL)
- •High-risk CR1 including:
- •Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23 rearrangements)
- •Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy
- •No CR within 4 weeks of initial treatment
- •Induction failure with ≤ 10% blasts in the marrow
- •CR2 or CR3
- •Myelodysplastic syndromes (MDS), Intermediate, High or Very High Risk by the revised international prognostic scoring system (IPSS-R)
- •Mixed Phenotypic Leukemia / Biphenotypic Leukemiain CR
- •Chronic Myelogenous Leukemia (CML) in second chronic phase after accelerated or blast crisis.
- •Myelofibrosis (MF):
- •Intermediate-1, Intermediate-2 or high risk by Dynamic International Prognostic Scoring System (DIPSS-plus) or
- •Monosomal karyotype or
- •Presence of inv(3)/i(17q) abnormalities or
- •Other unfavorable karyotype OR leukocytes ≥40 × 10(9) /L and
- •Circulating blasts ≤ 9%
- •Chronic Myelomonocytic Leukemia
- •Relapsed or Refractory Lymphoid Malignancies (including non-Hodgkin Lymphoma, Hodgkin Lymphoma and Chronic Lymphocytic Leukemia) meeting the following criteria:
- •Disease status: Stable Disease, Partial Remission or 2nd and 3rd Complete Remission. OR
- •Have relapsed after autologous transplant or who have failed to collect for an autologous transplant.
- •Age > 1 years, < 65yrs
- •KPS Performance status ≥80
- •Patients without a matched related or unrelated donor
- •Patient with either one or both:
- •Two 5/8 human leukocyte antigen (HLA) high resolution matched umbilical cord blood (UCB) grafts with a cell dose of 2.0x10^7 total number of nucleated cells per kilogram (TNC/kg) each, or
- •A related haplo-identical donor
- •Concurrent Therapy for Extramedullary Leukemia or central nervous system (CNS) Lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement. Maintenance therapy after transplant is allowed.
- •Subjects must have the ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Patients with inadequate Organ Function as defined by:
- •Creatinine clearance <50ml/min
- •Bilirubin > twice institutional upper limit of normal
- •aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) ≥ three times institutional upper limit of normal
- •Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≥ three times institutional upper limit of normal
- •Pulmonary function: diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DLCOc) < 60% normal
- •Cardiac: left ventricular ejection fraction < 50%
- •Karnofsky Performance Statue (KPS) < 80
- •Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with Reduced Intensity Conditioning (RIC) have the significant potential for teratogenic or abortifacient effects.
- •Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
- •Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds
- •Presence of donor-specific antibodies against chosen graft source.
研究组 & 干预措施
Thiotepa + Fludarabine + Melphalan
Melphalan 100 mg/m2 on day -8 Thiotepa 10 mg/kg on day -7 Fludarabine 160 mg/m2 in divided doses given on days -6, -5, -4 and -3.
干预措施: Melphalan (Drug)
Thiotepa + Fludarabine + Melphalan
Melphalan 100 mg/m2 on day -8 Thiotepa 10 mg/kg on day -7 Fludarabine 160 mg/m2 in divided doses given on days -6, -5, -4 and -3.
干预措施: Thiotepa (Drug)
Thiotepa + Fludarabine + Melphalan
Melphalan 100 mg/m2 on day -8 Thiotepa 10 mg/kg on day -7 Fludarabine 160 mg/m2 in divided doses given on days -6, -5, -4 and -3.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Percentage of Patients With Disease Free Survival
时间窗: Up to 1 year after transplant
Leukemia Free Survival (LFS) at 1 year is the percentage of patients alive and without evidence of hematologic malignancy at 1 year after transplant.
Percentage of Patients With Leukemia Free Survival
时间窗: Up to 1 year after transplant
次要结局
- Incidence of Acute GVHD(Up to 1 year after transplant)
- Rate of Neutrophil Engraftment(Up to 1 year after transplant)
- Average Overall Survival(Up to 1 year after transplant)
- Relapse Incidence(Up to 1 year after transplant)
- Treatment Related Mortality(Up to 1 year after transplant)
- Incidence of Chronic GVHD(Up to 1 year after transplant)
- Rate of Platelet Engraftment(Up to 1 year after transplant)