Phase II Study of Ibrutinib in Combination With Ixazomib in Patients With Waldenström Macroglobulinemia
概览
- 阶段
- 2 期
- 干预措施
- Ibrutinib
- 疾病 / 适应症
- Recurrent Waldenstrom Macroglobulinemia
- 发起方
- Mayo Clinic
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Complete Response Rate (CR)
- 状态
- 终止
- 最后更新
- 上个月
概览
简要总结
This phase II trial studies the side effects of ibrutinib citrate when given with ixazomib, and determines how well they work in treating patients with Waldenstrom macroglobulinemia that is newly diagnosed, has come back (recurrent) or does not respond to treatment (refractory). Enzyme inhibitors, such as ibrutinib and ixazomib citrate, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE: I. To determine the efficacy (as assessed by complete response \[CR\] rate) of the combination of ixazomib citrate (ixazomib) and ibrutinib in Waldenstrom macroglobulinemia (WM) patients. SECONDARY OBJECTIVES: I. To assess the overall response rate (ORR=partial response \[PR\] or better) in WM patients treated with ixazomib and ibrutinib. II. To assess the time to progression (TTP) in WM patients treated with ixazomib and ibrutinib. III. To further characterize the safety and toxicity of the combination of ibrutinib and ixazomib. IV. To assess the overall survival (OS) in WM patients treated with ixazomib and ibrutinib. CORRELATIVE RESEARCH OBJECTIVES: I. To determine the role of members of the BTK signalosome in achievement or lack thereof of response to ibrutinib and ixazomib. II. To explore biologic effects of ibrutinib and ixazomib on microenvironment in WM and correlate with response to treatment. OUTLINE: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.
研究者
入排标准
入选标准
- •Histological confirmation of WM; patients may have newly diagnosed, relapsed, or refractory disease; (definition: newly diagnosed; patients previously untreated for WM, relapse; patients who have received prior treatment for WM and now have disease recurrence; refractory; patients who have received anti-WM therapy and are noted to have progressive disease while on therapy, or those patients who demonstrated disease progression within 6 months of the last anti-WM treatment); NOTE: Ibrutinib naïve patients are allowed; if previously treated with ibrutinib, subject must have reached a response of at least stable disease (SD) and cannot have progressed while on ibrutinib; if subject stopped taking ibrutinib for reasons other than progression, they cannot have progressed for at least 6 months post last dose of ibrutinib
- •Presence of measurable disease as defined by: presence of immunoglobulin M (IgM) paraprotein, measurable lymphadenopathy on imaging studies and/or physical exam, and/or bone marrow infiltration \> 10%
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
- •Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to registration)
- •Platelet count \>= 75,000/mm\^3 (obtained =\< 14 days prior to registration) (NOTE: platelet transfusions in order to help patients meet eligibility criteria are not allowed)
- •Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to registration)
- •Total bilirubin =\< 1.5 x upper limit of normal (ULN) unless due to Gilbert's syndrome, in which case the direct bilirubin must be =\< 1.5 x ULN (obtained =\< 14 days prior to registration)
- •Aspartate transaminase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (obtained =\< 14 days prior to registration)
- •Calculated creatinine clearance must be \>= 30 ml/min using the Cockcroft Gault formula (obtained =\< 14 days prior to registration)
- •Negative pregnancy test done at screening and =\< 3 days (72 hours) prior to registration, for women of childbearing potential
排除标准
- •Failure to have fully recovered (i.e., =\< grade 1 toxicity) from the reversible effects of prior treatment for WM
- •Major surgical procedure (including open biopsy, excluding central line intravenous (IV) and port-a-cath placement) within =\< 14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment
- •Radiotherapy =\< 14 days prior to registration; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
- •Systemic treatment, =\< 14 days before registration, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or St. John's wort
- •Systemic anti-cancer therapy or participation in other clinical trials, including those with other investigational agents not included in this trial, =\< 28 days of registration and throughout the duration of active treatment in this trial
- •Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not; prior bortezomib treatment is allowed as per: patients with prior exposure to bortezomib will be allowed if they do not have disease refractory to bortezomib)
- •Central nervous system involvement (Bing-Neel syndrome)
- •Infection requiring systemic antibiotic therapy or other serious infection =\< 7 days prior to registration
- •Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, serious cardiac arrhythmia requiring medication (other than adequately rate-controlled atrial fibrillation), symptomatic congestive heart failure, unstable angina, stroke/transient ischemic attack (TIA) within the past 6 months or myocardial infarction within the past 6 months
- •Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
研究组 & 干预措施
Treatment (ixazomib citrate, ibrutinib)
Patients receive ixazomib citrate PO on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Ibrutinib
Treatment (ixazomib citrate, ibrutinib)
Patients receive ixazomib citrate PO on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Ixazomib Citrate
Treatment (ixazomib citrate, ibrutinib)
Patients receive ixazomib citrate PO on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis
Treatment (ixazomib citrate, ibrutinib)
Patients receive ixazomib citrate PO on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacodynamic Study
Treatment (ixazomib citrate, ibrutinib)
Patients receive ixazomib citrate PO on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacokinetic Study
结局指标
主要结局
Complete Response Rate (CR)
时间窗: 4 years
Complete response rate to be defined as an objective status of CR at any time, where confirmation of the complete response status is required on two consecutive evaluations with a second immunofixation before calling the patient a CR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Categorized by Response Assessment Criteria as specified in Appendix III of the protocol.
次要结局
- Overall Response Rate(Up to 5 years)
- Progression-free Survival(From study registration to the earliest date of documentation of disease progression, assessed up to 5 years)
- Overall Survival(Up to 5 years)
- Number of Patients Experiencing Grade 3+ Adverse Effects (AE) Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0(Up to 5 years)