A Phase II Study of PNT2258 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 27
- 主要终点
- Overall Response Rate
研究概览
简要总结
This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a multi-center, nonrandomized, open label, phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma.
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
- •Histologically confirmed diffuse large B-cell lymphoma that is refractory to prior therapy or relapsed after prior therapy.
- •FDG PET-CT (disease) positive baseline scan with measurable disease.
- •The patient must have received prior therapy that included:
- •CD20-targeted therapy (for example, rituximab),
- •Alkylating agent (for example, cyclophosphomide), and
- •Steroid, unless the patient is steroid intolerant
- •Exposure to at least 1 or 2 (but no more than 3) prior systemic cytotoxic chemotherapeutic regimens.
- •Note: Only those subjects who are not eligible for high-dose chemotherapy and autologous stem cell transplant (HD-ASCT), or who refuse HD-ASCT, are eligible with exposure to only 1 prior cytotoxic chemotherapeutic regimen.
- •ECOG performance status of 0-
- •The patient must be a stable baseline with CTCAE grade ≤ 2 regarding any acute or chronic toxicity associated with prior therapy, and have discontinued prior anti-cancer therapy for ≥ 14 days prior to C1D1; mitomycin-C for at least 6 weeks prior to C1D1; SCT ≥ 2 months prior to C1D
- •Note: Palliative steroids for control of disease-related symptoms are allowed and maintenance hormone therapy is allowed.
- •Adequate organ function including:
- •Hematologic: ANC ≥ 0.5 x 10^9/L. and platelets ≥ 50 x 10^9/L.
- •Hepatic: Total Bilirubin ≤ 2 x ULN (patients with Gilbert's syndrome must have total bilirubin ≤ 3 x ULN) and serum transaminase levels ≤ 2.5 x ULN. In the case of known liver metastasis (i.e., radiological or biopsy documented), serum transaminase levels must be ≤ 5 x ULN.
- •Renal: Serum creatinine ≤ 2 x ULN, or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2 x ULN.
- •Willingness to: 1.) undergo pre-treatment biopsy to obtain adequate tissue for analysis (e.g., core needle, excisional or incisional tumor biopsy) or 2.) provide archived tumor (e.g., FFPE block) for analysis.
排除标准
- •Eligibility for high-dose chemotherapy (HDT) and stem cell transplant (SCT). Note: Subjects who progressed ≥ 2 months after HDT/SCT are eligible
- •Concurrent malignancies requiring treatment.
- •Primary mediastinal (thymic) large B-cell lymphoma
- •Symptomatic CNS or leptomeningeal involvement of lymphoma.
- •Concurrent clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram or laboratory finding that, in the opinion of the investigator, could adversely affect the safety of the patient or impair the assessment of the study results.
- •Signs or symptoms of heart failure characterized as greater than NYHA Class II or other significant cardiac abnormalities.
- •Pregnant or breast-feeding.
- •Prior exposure to PNT
- •Life expectancy less than 3 months.
研究组 & 干预措施
PNT2258
PNT2258 will be administered at 120 mg/m2 on days 1-5 of a 21-day cycle. Treatment may continue unless there is disease progression or the occurrence of unacceptable toxicity for a total of 8 "induction" cycles of therapy. Subjects with CR/CMR, PR/PMR or SD/NMR at the end-of-cycle 8 scan then receive ongoing PNT2258 therapy at a dose of 100 mg/m2 on days 1-4 of a 28 day cycle until progressive disease, the occurrence of unacceptable toxicity, non-compliance, voluntary withdrawal or if in the opinion of the investigator the subject is no longer benefiting from exposure to PNT2258.
干预措施: PNT2258 (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: 19 months
The proportion of patients with complete response (CR/complete metabolic response \[CMR\]) or partial response (PR/partial metabolic response \[PMR\]) according to the revised 2014 International Working Group (IWG) criteria for lymphoma (Cheson 2014)
次要结局
- Disease Control Rate(19 months)
- Progression-free Survival(19 months)
- Time to Response(19 months)
- Safety - Assessment of Adverse Events(36 months)
- Duration of Overall Response(19 months)
- Overall Survival(19 months)