NCT02320487已完成2 期
A Phase II, Open-Label Study of Obinutuzumab Plus Bendamustine (BG) in Patients With Previously Untreated Chronic Lymphocytic Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 26
- 主要终点
- Percentage of Participants With Complete Response (CR), as Determined by the Investigator Using International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (iwCLL NCI-WG) Guidelines
研究概览
简要总结
This is a Phase 2, open-label, multicenter study to evaluate the safety and efficacy of BG induction therapy in participants with previously untreated CLL. The anticipated time on study treatment is 24 weeks.
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
- •Participants must satisfy one of the criteria for treatment initiation, as outlined in the iwCLL NCI-WG guidelines. The criteria include: (a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia, (b) Massive (i.e., greater than or equal to [>=] 6 centimeters [cm] below the left costal margin) or progressive or symptomatic splenomegaly, (c) Massive nodes (i.e., >= 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy, (d) Progressive lymphocytosis with an increase of greater than (>) 50 percent (%) over a 2-month period or lymphocyte doubling time (LDT) of less than (<) 6 months, (e) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, (f) Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of >=10% within the previous 6 months, significant fatigue (i.e., Eastern Cooperative Oncology Group Performance Status [ECOG PS] of 2 or worse or the inability to work or perform usual activities), fevers higher than 100.5 degrees Fahrenheit (°F)/38.0 degrees Celsius (°C) for >= 2 weeks without other evidence of infection, or night sweats for >1 month without evidence of infection
- •Absolute neutrophil count (ANC) >=1.5 × 10^9 per liter (/L) and platelets >=75 × 10^9/L unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g., myelodysplastic syndrome, hypoplastic bone marrow)
- •Life expectancy >6 months
- •ECOG PS of 0, 1, or 2
- •Willing to use acceptable contraceptive measures as defined by the protocol during and at least for 6 months (male participants) or 12 months (female participants) after the last dose of study drug
排除标准
- •Pregnant or lactating, or intending to become pregnant during the study: Women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
- •Participants who have received previous CLL therapy, including investigational therapies
- •Transformation of CLL to aggressive non-Hodgkin's lymphoma (Richter's transformation)
- •Inadequate renal function
- •Inadequate liver function: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3 liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >5× upper limit of normal [ULN] for >2 weeks; bilirubin >3× ULN) unless due to underlying disease
- •History of other malignancy, which could affect compliance with the protocol or interpretation of results
- •Participants with active bacterial, viral, or fungal infection requiring systemic treatment
- •Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)
- •Positive hepatitis serology: (a) Participants with positive serology for hepatitis B, defined as positivity for hepatitis B surface antigen (HBsAg), or participants who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive, (b) Participants positive for anti-HBc, but with negative hepatitis B Virus (HBV) deoxyribonucleic acid (DNA), will be considered for inclusion by the Medical Monitor on a case-by-case basis in order to ensure feasibility of monthly DNA testing and availability of appropriate care in case of hepatitis B reactivation, (c) Participants with positive serology for hepatitis C (HCV) unless HCV (by ribonucleic acid [RNA]) is confirmed negative
- •History of severe allergic or anaphylactic reactions to monoclonal antibodies
- •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of symptomatic bronchospasm)
- •Vaccination with a live vaccine a minimum of 30 days prior to study treatment
- •Use of investigational agents of any kind within 30 days before study treatment
研究组 & 干预措施
Obinutuzumab + Bendamustine (BG)
Experimental
Participants received obinutuzumab + bendamustine (BG) induction therapy in 28-day cycles for 6 cycles.
干预措施: Bendamustine (Drug)
Obinutuzumab + Bendamustine (BG)
Experimental
Participants received obinutuzumab + bendamustine (BG) induction therapy in 28-day cycles for 6 cycles.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Percentage of Participants With Complete Response (CR), as Determined by the Investigator Using International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (iwCLL NCI-WG) Guidelines
时间窗: 2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days)
The CR rate was defined as CR or CR with incomplete blood count recovery (CRi), assessed by the investigator according to iwCLL NCI-WG criteria. The definition of confirmed CR required all of the following criteria as assessed at least 2 months after completion of therapy: peripheral blood lymphocytes \< 4 times 10\^9 cells/L; absence of significant lymphadenopathy, hepatomegaly, or splenomegaly due to CLL involvement; absence of constitutional symptoms; normal complete blood count (CBC) without need for transfusion or exogenous growth factors, as exhibited by neutrophils \>/= 1.5 times 10\^9 cells/L, platelets \> 100 times 10\^9 cells/L, and hemoglobin \> 11.0 g/dL; normocellular BM aspirate with \< 30% lymphocytes; absence of lymphoid nodules; and BM biopsy without CLL activity. Those fulfilling CR criteria but who have persistent anemia, thrombocytopenia, or neutropenia were considered CRi.
次要结局
- Percentage of Participants With Objective Response of CR or Partial Response (PR) at the End of Induction Therapy, as Determined by the Investigator Using iwCLL NCI-WG Guidelines(2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days))
- Duration of Response Among Participants With Objective Response of CR or PR, as Determined by the Investigator Using iwCLL NCI-WG Guidelines(From the first assessment of CR, CRi, PR, or nPR (at up to approximately 228 to 258 days) until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months))
- Progression-Free Survival (PFS), as Determined by the Investigator Using iwCLL NCI-WG Guidelines(Day 1 until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months))
- Overall Survival (OS)(Day 1 until death from any cause (up to 46 months))
- Percentage of Participants Who Achieved Minimal Residual Disease (MRD)-Negative Status in Bone Marrow at Any Time During the Study(Up to 46 months)
- Percentage of Participants Who Achieved MRD-Negative Status in Peripheral Blood at Any Time During the Study(Baseline up to 46 months)
- Time to MRD-Negative Status in Peripheral Blood(Baseline up to 46 months)
- Duration of MRD-Negativity in Peripheral Blood Among Participants Who Achieved MRD-Negative Status(Baseline up to 46 months)
- Minimum Observed Concentration (Ctrough) of Obinutuzumab After Cycle 2(Pre-infusion (0 hours) on Day 1 Cycle 3 (1 cycle = 28 days))
- Ctrough of Obinutuzumab After Cycle 4(Pre-infusion (0 hours) on Day 1 Cycle 5 (1 cycle = 28 days))
- Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score(Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days))
- Change From Baseline in the EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) Score(Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days))
- Number of Hospitalizations Due to Adverse Events (AEs)(Day 1 up to 46 months)
- Percentage of Participants With Adverse Events (AEs)(Day 1 up to 46 months)
研究者
研究点 (26)
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