A Phase I/II Multi-Center, Open Label Trial of the Safety and Efficacy of Fostamatinib in Patients With Relapsed/Refractory B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Overall Response Rate as Assessed According to the"Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
研究概览
简要总结
Patients: B-cell lymphoma, refractory, diffuse, nodular, mantle, other Phase I : Two groups of 6 patients, escalating dose tolerability- 28 days Phase II: Three groups of 16 patients (nodular, diffuse large cell, mantle cell plus others). Oral bid dosing with highest tolerable dose until toxicity, progression, or withdrawal
详细描述
This multicenter, open-label study of fostamatinib will take place in two phases.
Phase I Two cohorts, of 6 patients each, will be sequentially assigned to receive 200 mg (Cohort 1) and 250 mg (Cohort 2) PO bid of R788. Patients will be enrolled at 250 mg bid in Cohort 2 only if < 1/6 patients in Cohort 1 experience dose-limiting toxicity (DLT) during the initial 28-day treatment period. If 2 or more patients in Cohort 1 experience DLT during the initial 28-day treatment period, patients in Cohort 2 will receive 150 mg PO bid.
Patients who do not experience DLT or disease progression may continue treatment at the assigned dose level until disease progression, toxicity or withdrawal. Patients who experience DLT may resume treatment at a lower dose level (dose will be decreased by 50 mg) when the toxicity grade has decreased to ≤ 1. Once all patients in Phase I have completed 28 days of treatment, the optimal dose of fostamatinib, based on safety and anti-tumor activity, will be determined.
Phase II 48 additional patients, 3 groups of 16 patients each, will receive fostamatinib at the optimal biologic dose PO bid until tumor progression, limiting toxicity or withdrawal. Group 1 will consist of patients with diffuse large B-cell lymphoma (DLBCL), Group 2 will consist of patients with follicular lymphoma, and Group 3 will consist of patients with mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphomas, small lymphocytic lymphomas (SLL), and chronic lymphocytic leukemia (CLL).
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be > 18 years old.
- •Patients must be willing and able to give written informed consent by signing an IRB-approved Informed Consent Form prior to admission to this study and must fully understand the requirements of the study and be willing to comply with all study visits and assessments.
- •Patients with relapsed/refractory B-cell malignancy, (DLBCL, follicular lymphoma, mantle cell lymphoma, MALT lymphoma, marginal zone lymphoma, CLL or SLL), who have failed at least one prior treatment regimen and for whom no standard therapy exists; patients who are intolerant of standard therapy or who are not candidates for available standard therapy may also be included.
- •Patients must have measurable disease.
- •Patients may be male or female. Men, if sexually active, must agree to use at least one medically acceptable form of birth control for the duration of the study and for 30 days thereafter. Sexually active women of childbearing potential must have a negative serum pregnancy test, and agree to use two independent methods of birth control for the duration of the study and for 30 days thereafter.
排除标准
- •Patients with T-cell lymphoma or primary CNS lymphoma
- •Patients with a history of malignancy other than lymphoma, except basal cell carcinoma of the skin and in situ cervical carcinoma, if < 2 years since curative treatment
- •Chemotherapy within 4 weeks of Day 1 of treatment (6 weeks for mitomycin C and nitrosoureas)
- •Antibody therapy or lymphoma vaccine therapy within 6 weeks of Day 1
- •Radiotherapy within 2 weeks of Day 1, 4 weeks if to marrow-bearing sites (sternum, pelvis)
- •Any other investigational therapy within 4 weeks of Day 1
- •Significant gastrointestinal disease (Crohn's or ulcerative colitis) or major gastric or small bowel surgery
- •Difficulty swallowing or malabsorption
- •Patients with bone marrow impairment: Hgb < 9.0 g/dL; ANC < 1500/μL; platelets < 75,000/μL
- •Patients with impairment of renal function: creatinine > 2.0 g/dL
- •Patients with abnormal liver function: AST/ALT > 3x ULN (up to 5x ULN with liver involvement); bilirubin > 1.5 mg/dL
- •Patients who have been treated with a CYP3A4 inducer/inhibitor within 1 week prior to Day 1 or who are expected to require treatment with CYP3A4 inducer/inhibitor during the course of the study (Appendix IV)
- •Patients with Karnofsky performance status < 60% (Appendix I)
- •Patients whose life expectancy is < 3 months
- •Patients who are known to be HIV positive
- •Patients who have a history of any other significant medical or physical condition that might impair the patient's well being or preclude full participation in the study
- •Pregnant or nursing females
- •Patients receiving systemic or chronic inhaled steroids, with the exception of intermittent dexamethasone for the treatment of emesis or intermittent steroid inhalers for exacerbations of asthma
研究组 & 干预措施
fostamatinib
干预措施: fostamatinib (Drug)
结局指标
主要结局
Overall Response Rate as Assessed According to the"Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
时间窗: Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response . (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)
Proportion of patients with Complete Response (CR) or Partial Response (PR). Revised Response Criteria for Malignant Lymphoma categorises the response of the treatment of a patient's tumour to; CR: the disappearance of all evidence of disease; PR: ≥ 50% decrease in the sum of the perpendicular diameters (SPD) of the six largest dominant nodes plus no increase in the size of other nodes and no new sites of disease; Stable Disease (SD): less than a PR but not progressive disease; Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Primary efficacy is based on Phase II patients only.
Clinical Benefit Rate as Assessed According to the "Revised Response Criteria for Malignant Lymphoma" (Cheson 2007).
时间窗: Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days)
Proportion of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD)
次要结局
- Progression Free Survival (PFS)(Serial tumor assessments were taken at baseline (within 28 days of the start of treatment), and re-evaluated at Day 57, and every 12 weeks thereafter or to confirm response (Maximum duration of treatment 511 days, Maximum duration of follow-up 812 Days))
- Overall Survival (OS)(Overall survival is measured from the time of first administration of study drug to death. (Maximum duration of treatment 511days, Maximum duration of follow-up 812 Days))