NCT01644253终止1 期
Phase 1b, Open Label Study to Evaluate Safety and Efficacy of TRU-016 in Combination With Rituximab, Obinutuzumab, Rituximab and Idelalisib, or Ibrutinib in Chronic Lymphocytic Leukemia and With Bendamustine in Peripheral T-cell Lymphoma
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 87
- 试验地点
- 8
- 主要终点
- CLL Cysteine 481 mutation status
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of TRU-016 in combination with rituximab, in combination with obinutuzumab, in combination with rituximab and idelalisib, or in combination with ibrutinib in patients with CLL; and in combination with bendamustine in patients with PTCL.
详细描述
The study will consist of 8 dose cohorts:
- Previously untreated patients 20 mg/kg TRU-016 + rituximab.
- Relapsed patients, 20 mg/kg TRU-016 + rituximab.
- Previously untreated patients 10 mg/kg TRU-016 + rituximab.
- Previously untreated patients TRU-016 + obinutuzumab.
- Relapsed patients, 20 mg/kg TRU-016 + rituximab + idelalisib.
- Patients with CLL on ibrutinib or another BTK inhibitor for a total of more than 1 year who have not had a complete response (CR) will continue receiving ibrutinib or another BTK inhibitor.
- Patients with CLL on ibrutinib or another BTK inhibitor with stable disease and in whom the cysteine 481 mutant clone is present at a level >1%, will continue receiving ibrutinib or the alternative BTK inhibitor.
- Patients with relapsed or refractory PTCL will receive TRU-016 dosed 10 mg/kg for the first dose and then 20 mg/kg weekly for 2 cycles, followed by dosing every other week for an additional 4 cycles (cycle = 28 days) + bendamustine for 2 days every cycle for 6 cycles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •* Diagnosis of CLL by 2008 IWCLL criteria and with Rai stage intermediate or high risk CLL. Cohort 8 patients must have a diagnosis of PTCL.
- •* No prior therapy for CLL for Cohorts 1, 3 and 4. For Cohort 2, 1-3 prior treatments. For Cohort 5, patients must have failed to respond or relapsed after 1 or more treatment regimens. For Cohort 6, patients who have been receiving ibrutinib for at least 12 months, have not had a CR, and in whom no cysteine 481 mutation is detected. For Cohort 7, patients who are receiving ibrutinib with stable disease and now have the cysteine 481 mutant clone present at levels of \>1%. For Cohort 8, have refractory or relapsed PTCL after one or more prior therapies.
- •* At least one of the following criteria for active disease requiring treatment: progressive splenomegaly and/or lymphadenopathy; anemia or thrombocytopenia due to bone marrow involvement; or progressive lymphocytosis with an increase of \>50% over a 2-month period or an unanticipated doubling time of less than 6 months
- •* For Cohorts 1, 3 and 4, contraindication to chemotherapy as first-line therapy due to patient age, comorbidity or patient preference
- •* Age \>/= to 18 years
- •* ECOG performance status of \ 6 months in opinion of Investigator
- •* Serum creatinine, total bilirubin, ALT/SGPT \/= 800/mm3, Cohort 8 (PTCL): ANC \>/= 1000/mm3
- •* Platelets \>/= 30,000/mm3
排除标准
- •For Cohorts 1, 3 and 4 only: Has received treatment with rituximab, alemtuzumab, ofatumumab or any other chemotherapeutic agent for CLL. Cohort 8: Received prior treatment with bendamustine and did not respond during treatment or relapsed less than sex months after completing treatment.
- •Has received an investigational therapy within 30 days of first dose of study drug
- •Previous or concurrent additional malignancy
- •Clinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune disease
- •Positive serology for HIV or hepatitis C
- •Hepatitis B surface antigen or hepatitis B core antibody positive
- •Pregnant or breastfeeding
- •Known current drug or alcohol abuse
研究组 & 干预措施
Cohort 2 - Relapsed CLL
Experimental
20 mg/kg TRU-016 + Rituximab
干预措施: 20 mg/kg TRU-016 + Rituximab (Biological)
Cohort 1 - Previously Untreated CLL
Experimental
20 mg/kg TRU-016 + Rituximab
干预措施: 20 mg/kg TRU-016 + Rituximab (Biological)
Cohort 3 - Previously Untreated CLL
Experimental
10 mg/kg TRU-016 + Rituximab
干预措施: 10 mg/kg TRU-016 + Rituximab (Biological)
Cohort 4 - Previously Untreated CLL
Experimental
20 mg/kg TRU-016 20 + Obinutuzumab
干预措施: TRU-016 20 mg/kg + Obinutuzumab (Biological)
Cohort 5 - Relapse CLL
Experimental
20 mg/kg TRU-016 + idelalisib + rituximab
干预措施: TRU-016 6-20 mg/kg + idelalisib + rituximab (Biological)
Cohort 6 - With CLL on ibrutinib with no complete response
Experimental
20 mg/kg TRU-016 + ibrutinib
干预措施: TRU-016 10-20 mg/kg + ibrutinib (Biological)
Cohort 7 - With CLL on ibrutinib with stable disease
Experimental
20 mg/kg TRU-016 + ibrutinib
干预措施: TRU-016 10-20 mg/kg + ibrutinib (Biological)
Cohort 8 - With relapsed or refractory PTCL
Experimental
20 mg/kg TRU-016 + 90 mg/m2 bendamustine
干预措施: TRU-016 10-20 mg/kg + bendamustine (Biological)
结局指标
主要结局
CLL Cysteine 481 mutation status
时间窗: CLL patients in Cohort 7 will be followed for 9 months unless no cysteine 481 mutation is detected.
The primary endpoint for Cohort 7 is the elimination of the cysteine 481 mutant clone (\<1%).
Incidence and severity of adverse events
时间窗: any time point during the study up to 18 months
次要结局
- Overall Response Rate (ORR)(any time point during the study up to 18 months)
- Duration of response (DOR)(any time point during the study up to 18 months)
- Area under the concentration-time curve (AUC0-t and AUC0-∞)(any time point during the study up to 12 months)
- Volume of distribution (Vd)(any time point during the study up to 12 months)
- Elimination half-life (t1/2)(any time point during the study up to 12 months)
- Overall survival (OS)(any time point during the study up to 18 months)
- Maximum serum drug concentration (Cmax)(any time point during the study up to 12 months)
- Minimum serum drug concentration (Cmin)(any time point during the study up to 12 months)
- Systemic clearance (CL)(any time point during the study up to 12 months)
- Progression-free survival (PFS)(any time point during the study up to 18 months)
- Resolution of disease-related symptoms(any time point during the study up to 18 months)
研究者
研究点 (8)
Loading locations...
相似试验
已完成
1 期
Safety and Efficacy Study of TRU-016 Plus Bendamustine vs. Bendamustine in Relapsed Chronic Lymphocytic LeukemiaChronic Lymphocytic Leukemia (CLL)NCT01188681Aptevo Therapeutics79
已完成
1 期
Phase 1/1b Study of TRU-016 in Patients With Previously Treated CLL or Select Subtypes of Non-Hodgkin's LymphomaChronic Lymphocytic Leukemia (CLL)Non-Hodgkin's Lymphoma (NHL)NCT00614042Aptevo Therapeutics96
终止
1 期
Safety Study of Rituximab (Rituxan®) in Chronic UrticariaUrticariaNCT00216762Johns Hopkins University15
已完成
1 期
Ruxolitinib in Combination With Trastuzumab in Metastatic HER2 Positive Breast CancerHER-2 Positive Breast CancerBreast CarcinomaMetastatic Breast CancerNCT02066532Dawn L. Hershman32
已完成
1 期
A Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent LymphomaB-cell Small Lymphocytic Lymphoma RecurrentNCT01317901Aptevo Therapeutics12