A Phase II Study of Microtransplantation in Patients With Refractory or Relapsed Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Number of Participants by Stratum Who Complete 2 Cycles of Therapy
研究概览
简要总结
Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation therapy, followed by an infusion of their donor's bone marrow or blood stem cells. The high-dose chemotherapy drugs and radiation are given to remove the leukemia cells in the body. The infusion of the donor's bone marrow or blood stem cells is given to replace the diseased bone marrow destroyed by the chemotherapy and/or radiation therapy. However, there are risks associated with allogeneic transplant. Many people have life-threatening or even fatal complications, like severe infections and a condition called graft-versus-host disease, which is caused when cells from the donor attack the normal tissue of the transplant patient.
Recently, several hospitals around the world have been using a different type of allogeneic transplant called a microtransplant. In this type of transplant, the donor is usually a family member who is not an exact match. In a microtransplant, leukemia patients get lower doses of chemotherapy than are used in traditional allogeneic transplants. The chemotherapy is followed by an infusion of their donor's peripheral blood stem cells. The objective of the microtransplant is to suppress the bone marrow by giving just enough chemotherapy to allow the donor cells to temporarily engraft (implant), but only at very low levels. The hope is that the donor cells will cause the body to mount an immunologic attack against the leukemia, generating a response called the "graft-versus-leukemia" effect or "graft-versus-cancer" effect, without causing the potentially serious complication of graft-versus-host disease.
With this research study, the investigators hope to find out whether or not microtransplantation will be a safe and effective treatment for children, adolescents and young adults with relapsed or refractory hematologic malignancies
详细描述
PRIMARY OBJECTIVES:
- To assess the safety and feasibility of standard chemotherapy plus GCSF-mobilized Hematopoietic Progenitor Cell, Apheresis (HPC-A) in pediatric patients with relapsed or refractory hematologic malignancies.
- To estimate the response rates to standard chemotherapy plus GCSF-mobilized HPC-A in pediatric patients with relapsed or refractory hematologic malignancies.
SECONDARY OBJECTIVES:
- To describe the event-free and overall survival of patients treated with standard chemotherapy plus GCSF-mobilized HPC-A.
- To estimate the time to neutrophil and platelet recovery after treatment with standard chemotherapy plus GCSF-mobilized HPC-A.
- To determine the cumulative incidence of acute and chronic graft-versus-host disease (GVHD).
OTHER PRESPECIFIED OBJECTIVES:
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Myeloid Malignancies
Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).
Interventions:
- Cycle 1: cytarabine, HPC-A donor infusion
- Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion
干预措施: Cytarabine (Drug)
Myeloid Malignancies
Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).
Interventions:
- Cycle 1: cytarabine, HPC-A donor infusion
- Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion
干预措施: Intrathecal Triples (Drug)
Myeloid Malignancies
Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).
Interventions:
- Cycle 1: cytarabine, HPC-A donor infusion
- Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion
干预措施: HPC-A (Biological)
结局指标
主要结局
Number of Participants by Stratum Who Complete 2 Cycles of Therapy
时间窗: At the end of therapy cycle 2 (approximately 2-3 months)
If two or more patients die from causes other than leukemia progression or experience ≥ Grade 3 GVHD that is associated with detectable donor chimerism due to this protocol, or demonstrate persistent engraftment defined as \>5% donor chimerism at the time of count recovery (ANC \> 0.3 x 10\^9/L and platelet count \> 30 x 10\^/L), then the cohort will close due to intolerability. Any subject who transfers to transplant prior to completion of two courses without experiencing an unacceptable toxicity is considered inevaluable for purposes of evaluating tolerability. Accrual will be halted for intolerability if there are two or more failures in tolerability among the first six subjects who are evaluable for tolerability.
Proportion of Participants Who Experience Therapeutic Success
时间窗: At the end of therapy cycle 2 (approximately 2-3 months)
All patients will be counted towards this two-stage design. Therapeutic success for patients at time of enrollment is defined as: * Patients with fewer than 5% blasts, a ≥ 10-fold decrease in level of minimal residual disease after completion of 1 or 2 cycles of therapy. * Patients with greater than 5% in leukemic blasts in the marrow, achieving CR or CRi after completion of 1 or 2 cycles of therapy. In terms of efficacy, patients who die before achieving therapeutic success will be counted as a failure, and all patients who receive ≥ 1 dose of protocol chemotherapy will be counted as a failure or success. Only subjects who withdraw or die prior to receiving the first dose of protocol chemotherapy will be considered inevaluable and replaced. The evaluation of tolerability and this phase II design will be performed concurrently, i.e., the first enrollees will be counted for both tolerability and efficacy.
次要结局
- 3-year Overall Survival (OS)(3 years after enrollment of the last participant)
- 3-year Event Free Survival (EFS)(3 years after enrollment of the last participant)
- Median Time to Neutrophil Recovery(From start of therapy to completion of therapy (approximately 1 year))
- Time to Platelet Recovery(From start of therapy to completion of therapy (approximately 1 year))
- 1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD)(From start of therapy through completion of therapy (approximately 1 year))
- 1-year Cumulative Incidence of Chronic Graft Versus Host Disease (GVHD)(From start of therapy through completion of therapy (approximately 1 year))