Phase II Study of UCN-01 in Relapsed or Refractory Systemic Anaplastic Large Cell and Mature T-Cell Lymphomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study will examine the effects of an experimental drug called UCN-01 (7-hydroxystaurosporine) on T-cell lymphomas. UCN-01 inhibits the growth of several different tumor cells, and, in laboratory studies, it has worked particularly well on tumor cells taken from patients with T cell lymphomas.
Patients 9 years of age and older with T cell lymphoma that has relapsed or is not responding to chemotherapy may be eligible for this study. Candidates will be screened with a medical histories and physical examinations, blood and urine tests, electrocardiograms, chest x-rays, and computed tomography (CT) scans of the chest, abdomen and pelvis. Additional tests may be done if clinically indicated, such as positron emission tomography (PET) scans, bone marrow aspirations and biopsies, lumbar punctures (spinal taps) and CT's or magnetic resonance imaging (MRI) scans if there is evidence of central nervous system disease.
Participants are given UCN-01 in 28-day treatment cycles. The drug is given by vein in a continuous 72-hour infusion on the first cycle and in 36-hour infusions on subsequent cycles. The total number of cycles patients receive depends on how well the tumor responds to the drug and how well the patient tolerates drug side effects. Patients who do well may receive treatment for up to 1 year. Patients whose disease worsens with treatment or who do not tolerate the therapy are taken off the study.
Some or all of the screening tests are repeated periodically during the course of treatment to monitor safety and treatment response. X-rays and scans are done every other treatment cycle for the first 6 cycles and then, if the cancer is stable or improving, the interval between these imaging studies is lengthened to every 4 cycles. Patients whose tumors can be safely biopsied undergo this procedure before entering the study and 3 to 5 days after completing the first UCN-01 treatment. Biopsies requiring open surgery (e.g., in the chest or abdomen) are done only if absolutely necessary for medical care. Biopsy tissue, blood, and other fluids are analyzed for gene and protein studies related to lymphoma research.
详细描述
Background:
- UCN-01 (7-hydroxystaurosporine), a non-specific protein kinase C (PKC) inhibitor appears to have several mechanisms of action including protein kinase C (PKC) isoenzyme inhibition and cyclin dependent kinase activation and inhibition.
- We have demonstrated that cell lines derived from T-cell lymphomas, including those with the t (2; 5) translocation, are very sensitive to UCN-01. The t (2; 5) translocation, associated with three quarters of cases of anaplastic large cell lymphomas (ALCL), is an oncogenic fusion protein - nucleophosmin-anaplastic lymphoma kinase (NPM-ALK).
- Anaplastic lymphoma receptor tyrosine kinase (ALK) is one potential target for UCN-01 action, and anaplastic large cell lymphoma (ALCL) derived SUDHL-1 cells containing the NPM-ALK protein have been shown to be very sensitive to UCN-01.
Objectives:
- To assess the clinical response to UCN-01 and progression-free and overall survival in patients with relapsed or refractory systemic Anaplastic Large Cell and other mature T-cell Lymphomas.
- To assess the effect of UCN-01 on ALK expression in ALCL cells.
- To assess the effect of UCN-01 on soluble tetrameric antibody complexes (TAC) (CD25).
- To evaluate mature T-cell lymphoma malignant cells by complimentary deoxyribonucleic acid (cDNA) microarray.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older 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
UCN-01 for T-cell lymphomas - Cohort 1 - Every 28 days
Cycle 1: 45 mg/m^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m^2
Cycle 2: 45 mg/m^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m^2; Repeat cycles every 28 days.
干预措施: UCN-01 (7-hydroxystaurosporine) (Drug)
UCN-01 for T-cell lymphomas - Cohort 2 -Every 21 days
Cycle 1: 45 mg/m^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m^2
Cycle 2: 45 mg/m^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m^2; Repeat cycles every 21 days.
干预措施: UCN-01 (7-hydroxystaurosporine) (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: 55 months
OS is defined as the date of on-study to the date of death from any cause or last follow up.
Clinical Response Rate
时间窗: 74.5 months
Clinical Response Rate is the percentage of participants with a response assessed by the International Workshop to Standardize Response Criteria. Complete response (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed (CRu) is per CR criteria except that if a residual node is \>1.5cm, it must have regressed by \>75%. Partial response (PR) is no increase in size of nodes, liver or spleen. Progressive disease (PD) is a greater than or equal to 50% increase from nadir. Details re: response criteria, see the protocol link module
Progression Free Survival (PFS)
时间窗: 3.6 months
PFS is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression is assessed by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphomas and is defined as a ≥50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for partial response's or non-responders or appearance of any new lesion during or at the end of therapy.
次要结局
- Number of Participants With Adverse Events(76 months)
研究者
Wyndham Wilson, M.D.
Dr. Wyndham Wilson
National Cancer Institute (NCI)