A Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation
A Phase I Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation
Patients with refractory hematologic malignancies, including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. Novel therapeutic agents that target molecular signaling mechanisms and increase the sensitivity of leukemic cells to apoptosis may clearly play a role in this setting.
This study hypothesizes that interrupting the SDF-1/CXCR4 axis using the selective CXCR4 antagonist plerixafor may be useful as a leukemic stem cell mobilizing agent for patients who are refractory to standard dose chemotherapy and in relapse after an allogeneic transplant. This hypothesis is based on the dependence of leukemia cells on MSCs for survival signals as described above and on the preclinical data that suggest increased efficacy by antileukemia agents when leukemia cells are separated from MSCs.
In the present trial, the study proposes to add plerixafor to enhance the conditioning regimen cytotoxicity. At this time the goal is to determine the maximum tolerated dose (MTD) of plerixafor through the process of dose limiting toxicity (DLT) evaluation. Pharmacokinetic studies will be conducted. Additional studies will quantify and the content of leukemia cells and key regulatory and effector T cell populations in the bone marrow and blood before and after exposure to this medication.
If the observed outcomes of this trial are promising, it could serve as a platform on which to study further use of plerixafor as a complimentary agent with conditioning as well as other chemotherapeutic regimens for patients with relapsed or refractory hematologic malignancies.
研究概览
详细说明
This study will determine the following objectives:
- To determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of plerixafor in combination with fludarabine, thiotepa, and melphalan as a conditioning regimen for children and young adults undergoing a second allogeneic stem cell transplant (SCT) procedure.
The study determines the secondary objectives:
- To describe the pharmacokinetic properties of plerixafor in this study population
- To estimate the cumulative incidence of relapse and overall survival in study participants at one year after this second transplant procedure
Other exploratory objectives include:
- To study the correlation between the pharmacokinetic properties of plerixafor and key regulatory and effector T cell populations in blood before and after exposure to plerixafor.
- To evaluate the content of leukemia cells in bone marrow and in blood before and after exposure to plerixafor
- To evaluate key regulatory and effector T cell populations in bone marrow and in blood before and after exposure to plerixafor
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Tennessee
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Memphis、Tennessee、美国、38105
- St. Jude Children's Research Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Age less than or equal to 21 years old.
- One of the following hematologic malignancies that has relapsed after prior allogeneic hematopoietic stem cell transplantation:
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
- Myelodysplastic syndrome (MDS)
- Chronic myeloid leukemia (CML)
- Juvenile myelomonocytic leukemia (JMML)
- Non-Hodgkin's lymphoma (NHL) with evidence of bone marrow disease
- Has a suitable human leukocyte antigen (HLA) matched family member or unrelated donor available for stem cell donation. A "matched" donor is defined as matching at 5/6 or 6/6 HLA loci.
- Does not have active central nervous system (CNS) malignancy (history of CNS disease allowed).
- No prior neuromuscular dysfunction or all prior grade I-IV neuromuscular dysfunctions have subsided > 4 weeks prior to enrollment.
- Cardiac shortening fraction greater than or equal to 25%.
- Creatinine clearance greater than or equal to 50 ml/min/1.73 m2
- Forced vital capacity (FVC) greater than or equal to 40% of predicted value or pulse oximetry greater than or equal to 92% on room air.
- Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 50 .
- Off all treatment for acute or chronic graft-versus-host disease (GVHD) for at least 7 days prior to the initiation of conditioning.
- Bilirubin less than or equal to 3 times the upper limit of normal for age.
- Alanine aminotransferase (ALT) less than or equal to 3.0 times the upper limit of normal for age.
- White blood cell count of less than 50,000/mm3
- Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
- Not lactating.
- All patients of childbearing potential must agree to use an effective birth control method
Exclusion Criteria:
- Pregnant and lactating females are excluded from participation as the short and long-term effects of the preparative agents and infusion on a fetus and a nursing child through breast milk are not entirely known at this time.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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其他：Second Allogeneic Transplant Procedure Recipient
Participants with Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Chronic Myeloid Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Non-Hodgkin lymphoma (NHL) with evidence of bone marrow disease, receiving a second allogeneic transplant procedure. Intervention: Plerixafor |
Plerixafor in combination with fludarabine, thiotepa and melphalan as a conditioning regimen for patients undergoing a second allogeneic transplant procedure (bone marrow or peripheral blood).
A traditional 3+3 phase I design will be employed during this study, where dose escalations are planned in groups of 3 participants.
No intra-participant escalation will be allowed and dose escalation will not be considered until toxicity information is available from at least 3 evaluable participants at the current dose level.Plerixafor will be given intravenously (IV) rather than subcutaneously (SQ) to minimize discomfort associated with repeated daily injections (up to 3) to the pediatric population of this study.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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To determine the dose-limiting toxicity and maximum tolerated dose of plerixafor in combination with fludarabine, thiotepa and melphalan as a conditioning regimen for patients undergoing a second allogeneic transplant procedure.
大体时间：7 days post transplant
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7 days post transplant
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
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