A Phase 1b Study Evaluating the Safety and Tolerability of ABT-199 in Combination With Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 49
- 试验地点
- 6
- 主要终点
- Assess the safety profile, to determine the maximum tolerated dose and Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab (R) in subjects with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma.
研究概览
简要总结
This is a Phase 1b, open-label, multicenter study evaluating the safety and tolerability of ABT-199 in combination with rituximab in up to 50 subjects with Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. The primary objectives of this study are to assess the safety profile, to determine the maximum tolerated dose and establish the Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab. The dose escalation portion of the study will include approximately 30 subjects. Once the recommended phase two dose and schedule have been determined, up to 20 additional subjects will be enrolled in an expanded safety portion of the study. Subjects who meet criteria for CR, CRi, or MRD-negative PR during the study may discontinue ABT 199. If disease progression occurs, as defined by iwCLL NCI/WG criteria for tumor response, or MRD progression, subjects may re-initiate ABT-199.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be greater then or equal to 18 years of age.
- •Subject must have relapsed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.
- •Subject has an Eastern Cooperative Oncology Group performance score of less than or equal to
- •Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
- •Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
排除标准
- •Chronic lymphocytic leukemia or Small Lymphocytic Lymphoma subject has undergone an allogeneic or autologous stem cell transplant.
- •Subject has uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
- •Subject has tested positive for human immunodeficiency virus.
- •Seropositivity for hepatitis B surface antigen or hepatitis C virus antibody or ribonucleic acid.
- •History of severe allergic or anaphylactic reactions to rituximab.
- •Subject has received a live viral vaccine within 6 months prior to the first dose of study drug.
- •Subject has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
- •Subject has received any of the following within 14 days prior to the first dose of study drug, or has not recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- •Any anti-cancer therapy including chemotherapy, immunotherapy, or radiotherapy;
- •Investigational therapy, including targeted small molecule agents.
- •Subject has a cardiovascular disability status of New York Heart Association Class greater then or equal to
- •Class 2 is defined as cardiac disease in which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain.
- •Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.
- •Subject has a history of other active malignancies other than CLL/SLL within the past 2 years prior to study entry, with the exception of:
- •Adequately treated in situ carcinoma of the cervix uteri;
- •Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- •Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- •Subject has malabsorption syndrome or other condition that precludes enteral route of administration.
- •Subject exhibits evidence of other clinically significant ongoing or recent condition(s) including, but not limited to:
- •Ongoing systemic infection (viral, bacterial, or fungal);
- •Diagnosis of fever and neutropenia within 1 week prior to study drug administration
研究组 & 干预措施
Arm 1
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
干预措施: ABT-199 (Drug)
Arm 1
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
干预措施: Rituximab (Drug)
结局指标
主要结局
Assess the safety profile, to determine the maximum tolerated dose and Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab (R) in subjects with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma.
时间窗: Continuous dosing at designated dose level up to Month 6. At end of combination treatment, ABT-199 monotherapy may continue up to 8 years following the date of the last subject enrolled. If disease progression occurs, subjects may re-initiate ABT-199.
Protocol-defined events, which are attributed as having a reasonable possibility of being related to the administration of ABT-199 and/or rituximab, or can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, underlying disease or concomitant medication, will be considered a dose limiting toxicity.
次要结局
- Determination of peak concentration (Cmax) of ABT-199 and/or Rituximab.(PK samples collected up to Month 6 for ABT-199 and Rituximab)
- Assess the exploratory efficacy of the combination ABT-199 and rituximab(Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.)
- Assess the exploratory efficacy of the combination ABT-199 and rituximab.(Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.)
- Determination of trough concentration (Ctrough) of ABT-199 and/or Rituximab(PK samples collected up to Month 6 for ABT-199 and Rituximab)
- Determination of area under the concentration versus time curve (AUC) of ABT-199 and/or Rituximab(PK samples collected up to Month 6 for ABT-199 and Rituximab)