A Multicenter, Open-Label, Single-Arm, Phase IIIb, International Study Evaluating the Safety of Obinutuzumab Alone or in Combination With Chemotherapy in Patients With Previously Untreated or Relapsed/Refractory Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 979
- 试验地点
- 174
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
This multicenter, open-label, single-arm study will evaluate the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in participants with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL). This is a Post-Authorization Safety Study. Participants will receive 6 cycles of single-agent obinutuzumab or obinutuzumab in combination with chemotherapy at the investigator's discretion. Each participant will be followed until 30 months after the last participant has been enrolled. Total length of the study is anticipated to be approximately 5 years.
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
- •Previously untreated documented CLL according to National Cancer Institute/international workshop on CLL (NCI/iwCLL) criteria OR relapsed and/or refractory documented CLL participants requiring treatment according to NCI/iwCLL criteria; participants with up to 3 relapses are eligible
- •Refractory participants if last treatment was with single-agent therapy, single-agent chemotherapy, or single-agent antibody
- •Participants with 17p-deletion and/or p53 mutation may be included at the investigator's discretion
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Life expectancy greater than (>) 6 months according to the investigator's opinion
- •Adequate hematological function
排除标准
- •Participants who have received more than 3 previous CLL treatment lines
- •Documented transformation of CLL to aggressive lymphoma (Richter's transformation)
- •Participants who are refractory to immunochemotherapy
- •Participants with abnormal laboratory values
- •One or more individual organ/system impairment score of 4 as assessed by the cumulative illness rating scale (CIRS) definition, excluding the eyes, ears, nose, throat and larynx organ systems
- •Participants with a history of progressive multifocal leukoencephalopathy (PML)
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- •Known hypersensitivity to the study drugs
- •History of prior malignancy unless the malignancy has been treated with a curative intent and in remission without treatment for greater than or equal to (>/=) 5 years prior to enrollment and with the exception of curatively-treated basal cell carcinoma, squamous cell carcinoma of the skin, low grade in situ carcinoma of the cervix, or low grade, early stage localized prostate cancer treated surgically with curative intent
- •Regular treatment with corticosteroids during the 28 days prior to the start of Cycle 1, Day 1, unless administered for indications other than CLL at a dose equivalent to less than or equal to (</=) 30 milligrams per day (mg/day) prednisone
- •Regular treatment with immunosuppressive medications following previous organ transplantation
- •Evidence of significant, uncontrolled concomitant diseases
- •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) or a major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization within 28 days prior to the start of Cycle 1, Day 1
- •Vaccination with live vaccines within 28 days prior to start of Cycle 1, Day 1
- •Major surgery (within 28 days prior to the start of Cycle 1, Day 1), other than for diagnosis
- •Positive for chronic hepatitis B, hepatitis C, human T-lymphotropic virus 1 (HTLV 1) or human immunodeficiency virus (HIV) infection
- •Pregnant or lactating women
- •Fertile men or women of childbearing potential
- •Participation in another clinical trial with drug intervention within 28 days prior to start of Cycle 1, Day 1 and during the study
研究组 & 干预措施
Obinutuzumab
Participants will receive obinutuzumab either alone as single agent or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.
干预措施: Bendamustine (Drug)
Obinutuzumab
Participants will receive obinutuzumab either alone as single agent or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.
干预措施: Chlorambucil (Drug)
Obinutuzumab
Participants will receive obinutuzumab either alone as single agent or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.
干预措施: Cyclophosphamide (Drug)
Obinutuzumab
Participants will receive obinutuzumab either alone as single agent or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.
干预措施: Fludarabine (Drug)
Obinutuzumab
Participants will receive obinutuzumab either alone as single agent or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: Baseline up to time of primary completion (3 years)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest and AEs of Particular Interest, were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Number of Participants With Adverse Events of Special Interest (AESIs)
时间窗: Baseline up to time of primary completion (3 years)
The following AEs were defined as AESIs: AEs with the preferred term Tumour Lysis Syndrome (TLS), Infusion-Related Reactions (IRRs) defined as AEs that occurred during or within 24 hours of the completion of obinutuzumab infusion and were assessed as related to obinutuzumab by the Investigator, Infections defined as AEs from System Organ Class (SOC) "Infections and infestations" and AEs with the preferred term Neutropenia. Reported are number of participants with total AESIs, IRRs, Infections, Neutropenia and TLS.
Number of Participants With Adverse Events of Particular Interest (AEPIs)
时间窗: Baseline up to time of primary completion (3 years)
The following AEs were defined as AEPIs: AEs with the preferred term Progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation defined as AEs with preferred term containing "Hepatitis B" or "hepatitis acute", thrombocytopenia defined via Roche MedDRA basket subgroup "haematopoietic thrombocytopenia", second malignancies defined as AEs from the SOC "Neoplasms benign, malignant and unspecified" starting 6 months after the first study drug intake, second malignancies based on standardised MedDRA queries (SMQ) starting 6 months after the first study drug intake based on the MedDRA SMQ "Malignant or unspecified tumours", in which benign neoplasms are not included, Cardiac events including AEs from the SOC "Cardiac disorders", and hemorrhagic events defined via Roche MedDRA basket subgroup "Haemorrhagic events". Reported are number of participants with total AEPIs and each of the AEPI categories.
次要结局
- Percentage of Participants With Minimal Residual Disease (MRD)-Negativity as Assessed by Flow Cytometry(3 months after the last dose of study treatment (up to approximately 5 years))
- Median Time to Response (TTR)(Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years))
- Median Time to Progression-Free Survival (PFS)(Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years))
- Percentage of Participants With Overall Response (OR) at Final Response Assessment (FRA)(3 months after the last dose of study treatment (up to approximately 5 years))
- Median Time to Duration of Response (DoR)(Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years))
- Percentage of Participants With Best Overall Response (BOR)(Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years))
- Median Time to New Anti-Leukemia Therapy (TTNT)(Baseline until end of study (up to approximately 5 years))
- Median Time to Event-Free Survival (EFS)(Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years))
- Median Time to Overall Survival (OS)(Baseline until death (Approximately up to 5 years))