Phase II Study of Ruxolitinib Maintenance Post-Hematopoietic Stem Cell Transplant in T-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Cumulative Incidence (CI) of relapse
研究概览
简要总结
This phase II trial tests how well ruxolitinib as a maintenance medication works to prevent relapse and graft-versus-host disease (GVHD) for patients who have undergone stem cell transplantation for T-cell lymphoma. GVHD is a common problem that may occur after a blood stem cell transplant. The "graft" is the donor blood cells that patients get during the transplant. The "host" is the person receiving the cells. GVHD is when the donor graft attacks and damages some of the transplant recipient's tissues. Ruxolitinib is a type of drug called a Janus kinase (JAK) inhibitor which works by decreasing the immune response of cells in the body. It is also a cancer growth blocker that blocks the growth factors that trigger the cancer cells to divide and grow. Ruxolitinib works by blocking a gene, called JAK2, that is important in the production of cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the effect of ruxolitinib phosphate (ruxolitinib) on relapse at 1-year after autologous (auto) stem cell transplant (SCT) in T-cell lymphoma (TCL).
II. Determine the effect of ruxolitinib on graft versus host disease (GvHD) and relapse free-survival (GRFS) at 1-year for allogeneic (allo) SCT in TCL.
SECONDARY OBJECTIVES:
PRIMARY 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with T-cell lymphoma [PTCL (all subtypes), T-PLL, ATLL, and CTCL (all subtypes)] in partial or complete remission between day +35 and +120 from auto-SCT or allo-SCT
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
- •Adequate hematologic function defined by absolute neutrophil count (ANC) > 1000/mm3 without granulocyte colony-stimulating factor (G-CSF) for at least 3 days, platelets > 50K/mm3 without transfusion for at least 3 days and hemoglobin (Hb) > 8.0 g/dL without transfusion for at least 3 days.
- •Adequate organ function defined by total Bilirubin < 1.5 x ULN, alanine aminotransferase (ALT) </= 3 x ULN, CKD-EPI eGFR ≥ 30 ml/min, SpO2 > 92% without supplemental oxygen.
- •Able to tolerate oral or enteral medications.
- •Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.
- •Able to read and sign informed consent.
排除标准
- •Anaplastic lymphoma kinase (ALK)+ or Dual specificity 22 (DUSP22)+ ALCL with low international prognostic index (IPI) score (<2) in first complete remission.
- •Progressive disease or any other systemic therapy post-SCT (radiation allowed)
- •Disease progression to Ruxolitinib previously
- •GvHD requiring systemic therapy.
- •Active uncontrolled infections.
- •Active thrombotic active microangiopathy requiring therapy.
- •History of veno-occlusive disorder post-transplant
- •Use of platelets antiaggregant or anticoagulants deemed to be unsafe to be held in case of thrombocytopenia.
- •History of life-threatening bleeding defined as any bleeding that required invasive procedures or involving central nervous system.
- •Pregnancy (positive Beta HCG test in a woman with childbearing potential defined as not postmenopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Uncontrolled Hepatitis B/C, HIV, tuberculosis, mycobacterium, or fungal infection.
- •Exposure to other investigational drugs within 4 weeks before enrollment.
- •Grade ≥ 3 non-hematologic toxicity from SCT that has not resolved to grade ≤
- •Myocardial infarction or stroke within 1 year of study entry.
- •Any uncontrolled medical problem at the discretion of the investigator that would pose a risk to the patient.
研究组 & 干预措施
Treatment (ruxolitinib maintenance)
Starting day +35 to day +120 post-SCT, patients receive ruxolitinib PO BID on days 1-30 of each cycle. Cycles repeat every 30 days for 1 year post-SCT, in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT scan and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or tissue biopsy throughout the study, at time of progression.
干预措施: Positron emission tomography-computed tomography (Procedure)
Treatment (ruxolitinib maintenance)
Starting day +35 to day +120 post-SCT, patients receive ruxolitinib PO BID on days 1-30 of each cycle. Cycles repeat every 30 days for 1 year post-SCT, in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT scan and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or tissue biopsy throughout the study, at time of progression.
干预措施: Bone Marrow Biopsy (Procedure)
Treatment (ruxolitinib maintenance)
Starting day +35 to day +120 post-SCT, patients receive ruxolitinib PO BID on days 1-30 of each cycle. Cycles repeat every 30 days for 1 year post-SCT, in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT scan and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or tissue biopsy throughout the study, at time of progression.
干预措施: Biopsy Procedure (Procedure)
Treatment (ruxolitinib maintenance)
Starting day +35 to day +120 post-SCT, patients receive ruxolitinib PO BID on days 1-30 of each cycle. Cycles repeat every 30 days for 1 year post-SCT, in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT scan and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or tissue biopsy throughout the study, at time of progression.
干预措施: Biospecimen Collection (Procedure)
Treatment (ruxolitinib maintenance)
Starting day +35 to day +120 post-SCT, patients receive ruxolitinib PO BID on days 1-30 of each cycle. Cycles repeat every 30 days for 1 year post-SCT, in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT scan and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or tissue biopsy throughout the study, at time of progression.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Cumulative Incidence (CI) of relapse
时间窗: at 1-year post-auto-SCT
Relapse is defined as evidence of disease progression or recurrence based on Lugano criteria or confirmed by biopsy.
GvHD and relapse free-survival (GRFS)
时间窗: at 1-year post-allo-SCT
GRFS is a composite endpoint of survival without grade III-IV acute GVHD, systemic therapy-requiring chronic GVHD (cGVHD), relapse, or death. Will be evaluated using the Kaplan-Meier method, with median survival and probability of surviving to relevant time points reported with point estimates and 90% confidence intervals separately for each study cohort. Comparisons to Center for International Blood and Marrow Transplant Research (CIBMTR) patients will use log-rank tests.
次要结局
- Progression-Free survival (PFS)(At 1 and 2 years)
- Overall Survival (OS)(At 1 and 2 years)
- Cumulative incidence of grade II-IV acute GVHD (allo-SCT cohort)(Up to 5 years)
- Cumulative incidence of chronic extensive GvHD (allo-SCT cohort)(at 1 year post-SCT)
- Cumulative Incidence of non-relapse mortality (NRM) at 1-year after (auto-SCT, allo-SCT, whole cohort)(At 1 year)
- Rates of grade 3-4 treatment Emergent Adverse Events(Up to 2 years)
- Rate of patients completing 1-year post-SCT maintenance Ruxolitinib(At 1 year post-SCT)
研究者
Jonathan Brammer
Principal Investigator
Ohio State University Comprehensive Cancer Center