Phase I/II, Open Label, Multicenter Study of Pacritinib Combined With Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Then maximum tolerated dose (MTD) of Pacritinib when given in combination with Ibrutinib
研究概览
简要总结
This study combines two drugs in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Investigators are proposing combining ibrutinib, an orally-administered, small molecule inhibitor of Bruton's tyrosine kinase (FDA approved for the treatment of relapsed/refractory CLL), with pacritinib, a novel JAK2-FLT3 inhibitor that has shown activity in relapsed lymphoma, including CLL/SLL. Investigators will first demonstrate the safety and tolerability of Pacritinib when combined with Ibrutinib in a phase I study, which will help establish the MTD (Maximum Tolerated Dose)of Pacritinib when combined with Ibrutinib. Once the optimal dose of Pacritinib is established in the phase I setting, a phase II evaluation will seek to establish the efficacy of the combination of Pacritinib with Ibrutinib. Patients will receive continuous treatment until progressive disease and will be followed while on study treatment for a total of 2 years.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CLL/SLL
- •Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy with active disease meeting criteria for treatment
- •Age ≥18 and <80
- •ECOG (Eastern Cooperative Oncology Group) ≤2 (This is a performance status that attempts to quantify a patients daily activities where 0 represents normal activity and 5 represents death)
- •Adequate organ function defined as AST and ALT ≤ 2 times upper limit of normal (ULN), Total Bilirubin ≤ 1.5 times ULN (exception of Gilbert disease), Renal function: CrCl ≥30 mL/min, Bazett-corrected Q-T interval ≤ 0.45 seconds
- •Peripheral blood counts of ANC >500 cells/μL, platelets ≥ 50,000 cells/ μL, Hemoglobin≥ 8 g/dL
- •Prior treatment allowed if: at least 30 days have elapsed since last chemotherapy and/or radiation and patient has recovered from all clinically significant treatment-related toxicity, or at least 90 days have passed since date of autologous stem cell transplant and patient has recovered to ≤grade 1 toxicity related to this procedure.
- •Ability to provide written informed consent
- •Ability to take oral medications.
排除标准
- •Pregnant or breast feeding women
- •Primary or metastatic CNS (Central Nervous System) disease prior to study enrollment
- •Uncontrolled current illness including, but not limited to, ongoing or active infections requiring intravenous antimicrobials, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia and/or psychiatric illness or social situations that would limit compliance with study requirements
- •Known HIV infection
- •Active infection with Hepatitis B or C virus
- •Concomitant therapy in last 30 days of any of the following: cytotoxic chemotherapy, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids
- •Prior treatment with ibrutinib
- •Uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP).
- •Requires anticoagulation with warfarin or equivalent Vit K antagonist
- •Allergy to either ibrutinib or pacritinib or components within medication
- •Treatment with strong CYP3A4 inducer or inhibitor, for which no alternative is available.
- •Unwilling or unable to use a medically acceptable form of contraception.
- •Any gastrointestinal or metabolic condition that could interfere with the absorption of oral medication.
研究组 & 干预措施
Pacritinib and Ibrutinib
Phase I: Patients will receive Pacritinib 100-200 mg twice daily along with Ibrutinib 420mg/day.
Phase II Lead-In: Pacritinib at MTD daily continuous x 2 months followed by Pacritinib at MTD twice daily along with Ibrutinib 420mg/day.
干预措施: Pacritinib (Drug)
Pacritinib and Ibrutinib
Phase I: Patients will receive Pacritinib 100-200 mg twice daily along with Ibrutinib 420mg/day.
Phase II Lead-In: Pacritinib at MTD daily continuous x 2 months followed by Pacritinib at MTD twice daily along with Ibrutinib 420mg/day.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Then maximum tolerated dose (MTD) of Pacritinib when given in combination with Ibrutinib
时间窗: 28 Days
DLTs (Dose Limiting Toxicities) occurring during the 1st cycle (first 28 days) of treatment with the combination of pacritinib and ibrutinib will be used for dose-escalation decisions. MTD is defined as the largest dose at which no more than 25% of patients experience a DLT.
The number of patients with a Complete Response (CR)
时间窗: 2 Years Post Treatment
Patients will be followed for response from the date of initial treatment until 2 years post treatment. CR is defined as: Lymphadenopathy - None ˃1.5 cm Hepatomegaly - None Splenomegaly - None Blood Lymphocytes - ˂ 4000/μL Bone Marrow - Normocellular, 30% lymphocytes, no B-lymphoid nodules. Platelet Count - ˃ 100,000/μL Hemoglobin - ˃ 11.0 g/dL Neutrophils - ˃ 1,500/μL
次要结局
未报告次要终点