A Phase Ib Single-arm, Open-label, Multicenter Study to Assess the Safety and Tolerability of Combined Treatment With Nilotinib 300mg BID and Ruxolitinib Increasing Dose in CML and Ph+ ALL Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Occurrence of dose limiting toxicities (DLTs)
研究概览
简要总结
In this study it was the rationale to evaluate the safety and tolerability of the combined administration of nilotinib and increasing dose of ruxolitinib in patients with chronic myeloid leukemia and patients with Philadelphia positive acute lymphoblastic leukemia.
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
- •Patients of the first stratum must have chronic myeloid leukemia receiving nilotinib first-line therapy or receiving second-line or subsequent-line treatment with nilotinib.
- •Patients of the second stratum must have CML in AP/BC or relapsed/refractory Ph+ ALL, or be Ph+ ALL patients with MRD with or without prior nilotinib pretreatment;
- •Patients must have adequate end organ function, as defined by:
- •Creatinine < 2.0 x upper limit of normal (ULN)
- •Total bilirubin < 1.5 x ULN (< 3.0 x ULN if related to disease or polymorphism, such as Mb. Gilbert)
- •ALT and AST < 2.5 x ULN (< 5.0 x ULN if related to disease)
- •Serum lipase ≤ 1.5 x ULN
- •Alkaline phosphatase ≤ 2.5 x ULN (< 5.0 x ULN if related to disease);
- •Patients must have the following electrolyte values within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication:
- •Potassium
- •Magnesium
- •Phosphate
- •Total calcium (corrected for serum albumin);
- •Female patients of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before initiation of study drug. All WOCBP must use highly effective contraceptive methods throughout and during 3 months after study;
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 for patients in CP, ≤ 2 for patients in AP/BC or with relapsed/refractory Ph+ ALL or with Ph+ ALL with MRD;
- •Patient has the following laboratory values within 7 days of starting study drug:
- •For CML and Ph+ ALL patients: platelet count > 75 x 109/L and ANC > 1.0 x 109/L
排除标准
- •Patient must not have evidence of active malignancy other than the existing CML or ALL
- •Patient must not receive drugs that interfere with coagulation or inhibits platelet function, with the exception of aspirin ≤ 150 mg per day or low molecular weight heparin.
- •Patient must not have history of platelet dysfunction, bleeding diathesis, and/or coagulopathy in the 6 months prior to screening;
- •Patient must not require treatment with any strong CYP3A4 inducer or inhibitor
- •Patient must not have history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes and their excipients;
- •Patients must not take other investigational drugs within 28 days prior to screening;
- •Patient must not be pregnant or lactating at screening and/or baseline;
- •Patient must not have impaired cardiac functions
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Nilotinib and Ruxolitinib
The study included two strata, which were to be treated in parallel. The first stratum consisted of CML-patients in CP, which had been on nilotinib treatment before entering the study. These patients did not optimally respond to the previous treatment. The second stratum consisted of patients with CML in AP or BC and patients with relapsed/refractory Ph+ ALL and Ph+ ALL patients with MRD, with or without previous nilotinib treatment. Patients were treated with 300mg nilotinib BID during the escalation phase (12 months) with increasing doses of ruxolitinib. The dose expansion phase (12 months) began following the determination of the MTD of the combination and the decision to explore the cohort for confirmation of RPIID. In this phase, safety and tolerability of the MTD and/or potential RPIID was to be further evaluated, with the purpose of establishing that this dose is suitable for use in this patient group.
干预措施: Nilotinib (Drug)
Nilotinib and Ruxolitinib
The study included two strata, which were to be treated in parallel. The first stratum consisted of CML-patients in CP, which had been on nilotinib treatment before entering the study. These patients did not optimally respond to the previous treatment. The second stratum consisted of patients with CML in AP or BC and patients with relapsed/refractory Ph+ ALL and Ph+ ALL patients with MRD, with or without previous nilotinib treatment. Patients were treated with 300mg nilotinib BID during the escalation phase (12 months) with increasing doses of ruxolitinib. The dose expansion phase (12 months) began following the determination of the MTD of the combination and the decision to explore the cohort for confirmation of RPIID. In this phase, safety and tolerability of the MTD and/or potential RPIID was to be further evaluated, with the purpose of establishing that this dose is suitable for use in this patient group.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Occurrence of dose limiting toxicities (DLTs)
时间窗: Baseline, up to day 28 (equals first cycle)
Occurrence of DLTs during cycle 1
次要结局
- Safety and tolerability profile of nilotinib and ruxolitinib administered in combination(Baseline, up to month 12)
- Trough levels of nilotinib and ruxolitinib administered in combination(Baseline, up to month 12)
- Clinical activity of nilotinib and ruxolitinib administered in combination(Baseline and at 3, 6, and 12 months)