A Study of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies
A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Edmonton、加拿大、T6G 1Z2
- Site Reference ID/Investigator# 8941
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California
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Los Angeles、California、美国、90033
- Site Reference ID/Investigator# 4997
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Los Angeles、California、美国、90095
- Site Reference ID/Investigator# 9104
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Maryland
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Bethesda、Maryland、美国、20892
- Site Reference ID/Investigator# 2613
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Massachusetts
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Boston、Massachusetts、美国、02215
- Site Reference ID/Investigator# 40243
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Boston、Massachusetts、美国、02215
- Site Reference ID/Investigator# 4745
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New York
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Buffalo、New York、美国、14263
- Site Reference ID/Investigator# 2628
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New York、New York、美国、10016
- Site Reference ID/Investigator# 23543
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New York、New York、美国、10021
- Site Reference ID/Investigator# 2627
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New York、New York、美国、10032
- Site Reference ID/Investigator# 2614
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New York、New York、美国、10065
- Site Reference ID/Investigator# 5383
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Rochester、New York、美国、14642
- Site Reference ID/Investigator# 12306
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Diagnoses:
- 1a/1b - lymphoid malignancy;
- 2a, Arm A - follicular lymphoma;
- 2a, Arm B - mantle cell, peripheral or cutaneous T-cell lymphomas including mycosis fungoides and Sezary syndrome or other indolent B-cell lymphomas such as marginal zone lymphoma;
- Received at least 1 prior chemotherapy treatment regimen (P1a/1b) and relapsed or refractory disease (P2a).
- Eastern Cooperative Oncology Group (ECOG) score of <= 1.
- Magnetic Resonance Imaging (MRI)/computed tomography (CT) negative for subdural or epidural hematoma w/in 28 days prior to first dose, if clinically indicated.
- Stable dose of Selective serotonin reuptake inhibitors (SSRI) antidepressants for at least 21 days prior to 1st dose.
Adequate bone marrow (BM) independent of any growth factor support (except with heavily infiltrated bone marrow (80% or more)):
- Absolute Neutrophil Count (ANC) >= 1000/µL;
- Platelets >= 100,000/mm3 (entry count must be independent of transfusion with in 14 days of Screening);
- Hemoglobin >= 9.0/dL.
Adequate coagulation, renal, and hepatic function:
- Serum creatinine <= 2.0 mg/dL or calculated creatinine clearance >= 50 mL/min;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0 x Upper Limit of Normal (ULN);
- Bilirubin <= 1.5 x ULN;
- Gilbert's Syndrome may have a bilirubin > 1.5 x ULN;
- Coagulation: Activated partial thromboplastin time (aPTT), Prothrombin Time (PT), not to exceed 1.2 x ULN
- Females must be surgically sterile, postmenopausal (at least 1 year), or negative results for a pregnancy test performed at Screening on a serum sample obtained with in 14 days prior to initial dose, and prior to dosing on a urine sample obtained on C1 D-3 (P1a) or Lead-in D1 (P1b, P2a) if > 7 days since serum results.
- Females not surgically sterile or postmenopausal (at least 1 year) and non-vasectomized males must practice birth control.
P2a only: History of autologous stem cell transplant must be > 6 months post transplant with adequate BM independent of growth factor support per lab reference range at Screening as follows:
- Absolute Neutrophil Count (ANC) >= 1,500/µL;
- Platelets >= 125,000/mm3 (entry platelet count must be independent of transfusion with in 14 days of Screening);
- Hemoglobin >= 10.0g/dL;
- Measurable disease by International Working Group (IWG)/National Cancer Institute- sponsored Working Group (NCI-WG) criteria.
At least one of following for Pharmacodynamics (P2a):
- archived diagnostic Formalin Fixed Paraffin Embedded (FFPE) tumor tissue with no intervening treatment since biopsy,
- core needle biopsy of malignant lymph node, or
- bone marrow aspirate or core positive for lymphoma.
Extension Study Inclusion Criteria Phase 2a subjects who enter the Extension Study must continue to meet all Inclusion and Exclusion criteria, with the exception of Inclusion Criterion regarding measurable disease by International Working Group (IWG)/National Cancer Institute- sponsored Working Group (NCI-WG) criteria and Inclusion Criteria regarding laboratory parameters for hematology, coagulation, and chemistry. Subjects entering the Extension Study must also have stable lab values per applicable laboratory reference ranges. In addition, subjects must also meet the following criteria:
Subjects must meet the following hematology and coagulation lab criteria:
- Platelet counts must be >= 25,000/mm3 (untransfused). Platelet counts <= 50,000/mm3 must be stable and monitored at an increased frequency at the discretion of the investigator.
- Absolute Neutrophil count (ANC) >= 500/µL. ANC >= 500/µL and < 1,000/µL should be monitored at an increased frequency at the discretion of the investigator.
- Hemoglobin of >= 8.0 g/dL.
- aPTT, PT is not to exceed 1.2 x ULN.
Chemistry values must not exceed Grade 2. Grade 2 chemistry labs should be monitored at an increased frequency at the discretion of the investigator. Subjects must meet the following chemistry criteria:
- Serum creatinine <= 3.0 x the upper normal limit (ULN) of institution's normal range. * AST and ALT <= 5.0 x the upper normal limit (ULN) of institution's normal range.
- Bilirubin <= 3.0 x ULN. Subjects with Gilbert's Syndrome may be allowed to have a Bilirubin > 3.0 x ULN based on a joint decision between the investigator and Abbott medical monitor.
Exclusion Criteria:
- History of, or is, clinically suspicious for cancer-related Central Nervous System (CNS) disease, lymphoid or non-lymphoid.
- Undergone an allogeneic or autologous stem cell transplant.
- Underlying, predisposing condition of bleeding or currently exhibits signs of clinically significant bleeding.
- Recent history of non-chemotherapy induced thrombocytopenic associated bleeding with in 1 year prior to first dose.
- Active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
- Active immune thrombocytopenic purpura or history of being refractory to platelet transfusions with in 1 year prior to first dose.
- Significant history of cardiovascular disease, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease.
- Females pregnant or breast-feeding.
- Positive for human immunodeficiency virus (HIV)
- History of other active malignancies with in the past 3 years (P1a/1b) or past 5 years (P2a), except adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma; in situ carcinoma of the bladder; previous malignancy confined and surgically resected with curative intent.
- Evidence of other clinically significant uncontrolled condition(s), including, but not limited to active systemic fungal infection; diagnosis of fever and neutropenia with in 1 week prior to study drug.
- Received steroid therapy with in 7 days prior to 1st dose of study drug for anti-neoplastic intent.
- Received any anti-cancer therapy, including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy, with in 14 days prior to first dose of study drug, or has not recovered to <Gr2 clinically significant AE(s) /toxicity(s) of the previous therapy.
- Received a biologic with in 30 days prior to first dose.
- Currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central venous catheter.
- Received aspirin with in 7 days prior to first dose and during ABT-263 administration.
- Consumed grapefruit or grapefruit products with in 3 days prior to first dose.
- P1a/1b only: Diagnosed with Posttransplant lymphoproliferative disorder (PTLD); Burkitt's, Burkitt-like, or HIV-associate lymphoma; lymphoblastic lymphoma/leukemia; or multiple myeloma.
- Subject has received CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 7 days prior to the administration of the first dose of ABT-263 (P2a).
- Subject had a prior significant toxicity from another Bcl-2 family protein inhibitor (P2a).
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:顺序分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Phase 1a and 1b
Relapsed or refractory lymphoid malignancies
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Oral solution Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing. Oral solution and tablets Phase 2a dosing under 21 day continuous dosing. - 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose. |
实验性的:Arm A (Phase 2a)
Relapsed or refractory follicular lymphoma
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Oral solution Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing. Oral solution and tablets Phase 2a dosing under 21 day continuous dosing. - 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose. |
实验性的:Arm B (Phase 2a)
Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma
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Oral solution Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing. Oral solution and tablets Phase 2a dosing under 21 day continuous dosing. - 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose. |
实验性的:Extension Study
Relapsed or refractory follicular lymphoma or Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma
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Oral solution Phase 1 dosing was under two different schedules: 14 days on drug, 7 days off or 21 days continuous dosing. Oral solution and tablets Phase 2a dosing under 21 day continuous dosing. - 150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose. |
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Phase 1a: Determine dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) and schedule - intermittent dosing.
大体时间:Repeating sequence of 14 days on therapy and 7 days off.
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1a: Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 14/21 day dosing schedule
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Repeating sequence of 14 days on therapy and 7 days off.
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Phase 1b: Determine dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) and schedule - continuous dosing.
大体时间:21 day continuous dosing.
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Phase 1b: Determination of ABT-263 dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 21 day continuous dosing schedule.
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21 day continuous dosing.
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Phase 2a: Continued assessment of safety profile at the recommended Phase 2 dose (RPTD) and schedule - continuous dosing.
大体时间:21 day continuous dosing.
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Phase 2a: Continued assessment of the safety profile of ABT-263 at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.
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21 day continuous dosing.
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Phase 2a: Assessment of preliminary efficacy signals including biomarker assessment - continuous dosing.
大体时间:21 day continuous dosing.
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Phase 2a: Assessment of the preliminary efficacy signals of ABT-263, including biomarker assessment, at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.
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21 day continuous dosing.
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Extension Study: Continued assessment of the safety profile of ABT-263
大体时间:21 day continuous dosing
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Continued assessment of the safety profile of ABT-263.
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21 day continuous dosing
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Extension Study: Continued assessment of the preliminary efficacy signals of ABT-263.
大体时间:day continuous dosing
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Continued assessment of the preliminary efficacy signals of ABT-263.
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day continuous dosing
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Phase 1a or Phase 1b safety assessment
大体时间:Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing.
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Assessment of the safety of ABT-263
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Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing.
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Phase 1a, Phase 1b, or Phase 2a pharmacokinetic profile evaluation
大体时间:Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing.
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Evaluation of pharmacokinetic profile of ABT-263.
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Repeating sequence of 14 days on therapy and 7 days off OR 21 day continuous dosing.
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Phase 1a effect of food on bioavailability
大体时间:Repeating sequence of 14 days on therapy and 7 days off.
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Evaluation of the effect of food on bioavailability
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Repeating sequence of 14 days on therapy and 7 days off.
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合作者和调查者
调查人员
- 研究主任:Mack Mabry, MD、AbbVie
出版物和有用的链接
一般刊物
- Wilson WH, O'Connor OA, Czuczman MS, LaCasce AS, Gerecitano JF, Leonard JP, Tulpule A, Dunleavy K, Xiong H, Chiu YL, Cui Y, Busman T, Elmore SW, Rosenberg SH, Krivoshik AP, Enschede SH, Humerickhouse RA. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010 Dec;11(12):1149-59. doi: 10.1016/S1470-2045(10)70261-8. Epub 2010 Nov 18.
- de Vos S, Leonard JP, Friedberg JW, Zain J, Dunleavy K, Humerickhouse R, Hayslip J, Pesko J, Wilson WH. Safety and efficacy of navitoclax, a BCL-2 and BCL-XL inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study. Leuk Lymphoma. 2021 Apr;62(4):810-818. doi: 10.1080/10428194.2020.1845332. Epub 2020 Nov 25.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- M06-814
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ABT-263的临床试验
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National Cancer Institute (NCI)终止难治性恶性实体瘤 | 复发性恶性实体瘤 | 转移性恶性实体瘤 | 不可切除的实体瘤 | 复发性肺小细胞癌 | IIIA 期肺癌小细胞癌 AJCC v7 | IIIB 期肺癌小细胞癌 AJCC v7 | IV 期肺小细胞癌 AJCC v7 | III 期肺小细胞癌,美国癌症联合委员会 (AJCC) v7美国
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AbbVie (prior sponsor, Abbott)完全的
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National Cancer Institute (NCI)主动,不招人IIIA 期肺癌非小细胞癌 AJCC v7 | 晚期肺非鳞状非小细胞癌 | 转移性肺非鳞状非小细胞癌 | IIIB 期肺癌非小细胞癌 AJCC v7 | IV 期肺癌非小细胞癌 AJCC v7 | III 期肺癌非小细胞癌 AJCC v7美国
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AbbVie主动,不招人骨髓纤维化 (MF)美国, 阿根廷, 澳大利亚, 巴西, 保加利亚, 智利, 匈牙利, 以色列, 意大利, 日本, 大韩民国, 西班牙, 瑞典, 火鸡
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City of Hope Medical CenterNational Cancer Institute (NCI)招聘中