NCT04608318进行中（未招募）3 期
A Phase 3 Multicentre, Randomized, Prospective, Open-label Trial of Ibrutinib Monotherapy Versus Fixed-duration Venetoclax Plus Obinutuzumab Versus Fixed-duration Ibrutinib Plus Venetoclax in Patients with Previously Untreated Chronic Lymphocytic Leukaemia (CLL)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 897
- 试验地点
- 180
- 主要终点
- Investigator-assessed progression-free survival (PFS)
研究概览
简要总结
The aim of this study is to compare the efficacy of continuous ibrutinib monotherapy with fixed-duration venetoclax plus obinutuzumab and fixed-duration ibrutinib plus venetoclax by measuring progression-free survival (PFS) in patients with previously untreated CLL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Documented CLL requiring treatment according to iwCLL criteria.
- •Age at least 18 years.
- •Life expectancy ≥ 6 months.
- •Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
- •Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of screening initiation as follows, unless cytopenia is due to CLL:
- •Absolute neutrophil count ≥ 1.0 × 109/L
- •Platelet counts ≥ 30 × 109/L; in cases of thrombocytopenia clearly due to CLL (per the discretion of the investigator), platelet count should be ≥ 10 × 109/L
- •Total haemoglobin ≥ 8 g/dL (without transfusion support, unless anaemia is due to CLL)
- •GFR >30ml/min directly measured with 24hr urine collection, calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight)/ (72 x creatinine), for women x 0, 85) or an equally accurate method.
- •a. For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 30 ml/min may be eligible if a repeat estimate after adequate hydration is > 30 ml/min.
- •Adequate liver function as indicated by a total bilirubin ≤ 2 x, AST/ ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome.
- •Negative serological testing for hepatitis B (HbsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month/every three months if persistently negative until 12 months after last treatment cycle), and for hepatitis C (anti-HCV-ab negative; in case of positive HCV anti-body test, negative HCV-PCR is required).
- •Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-
- •Exclusion criteria:
- •Any prior CLL-specific therapies (except corticosteroid treatment administered due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents up to 20 mg prednisolone are permitted).
- •Transformation of CLL (Richter transformation). When Richter transformation is suspected, PET-CT and/or biopsy should be performed to rule out transformation.
- •Patients with a history of PML.
- •An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the study treatment or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could compromise the patients' safety or interfere with the absorption or metabolism of the study drugs (e.g. inability to swallow tablets or impaired resorption in the gastrointestinal tract).
- •Malignancies other than CLL currently requiring systemic therapies, not being treated with curative intent before (unless the malignant disease is in a stable remission due to the discretion of the treating physician or showing signs of progression after curative treatment.
- •Uncontrolled or active infection.
- •Patients with known infection with human immunodeficiency virus (HIV).
- •Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/ inducers (incl. up to 7 days prior to study treatment start).
- •Anticoagulant therapy with warfarin, phenprocoumon or other vit-amin K antagonists (alternative anticoagulation is allowed (e.g. DOACs), but patients must be properly informed about the potential risk of bleeding under treatment with ibrutinib).
- •History of stroke or intracranial hemorrhage within 6 months prior to registration for study screening.
- •Known bleeding disorders
- •Child B / C liver cirrhosis
- •Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening.
- •Vaccination with live vaccines 28 days prior to registration for study screening.
- •Major surgery less than 30 days before start of study treatment.
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products.
- •Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
- •Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of study treatment; further pregnancy testing will be performed monthly).
- •Fertile men or women of childbearing potential unless:
- •surgically sterile or ≥ 2 years after the onset of menopause
- •willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment.
- •Legal incapacity.
- •Prisoners or subjects who are institutionalized by regulatory or court order.
- •Persons who are in dependence to the sponsor or an investigator.
排除标准
- 未提供
研究组 & 干预措施
I (Ibrutinib)
Experimental
Ibrutinib p.o. will be administered until occurrence of unacceptable toxicity, progression of CLL or end of trial, whichever occurs first.
干预措施: Ibrutinib (Biological)
VG (Obinutuzumab + Venetoclax)
Experimental
12 cycles (q 28d): Obinutuzumab i.v. + Venetoclax p.o. will be administered for 6 cycles, followed by 6 additional cycles of Venetoclax alone
干预措施: Venetoclax (Biological)
VG (Obinutuzumab + Venetoclax)
Experimental
12 cycles (q 28d): Obinutuzumab i.v. + Venetoclax p.o. will be administered for 6 cycles, followed by 6 additional cycles of Venetoclax alone
干预措施: Obinutuzumab (Biological)
VI (Venetoclax + Ibrutinib)
Experimental
15 cycles (q 28d): Ibrutinib p.o. + Venetoclax p.o. will be administered for a total of 12 cycles with a prior Ibrutinib monotherapy lead-in of 3 cycles
干预措施: Ibrutinib (Biological)
VI (Venetoclax + Ibrutinib)
Experimental
15 cycles (q 28d): Ibrutinib p.o. + Venetoclax p.o. will be administered for a total of 12 cycles with a prior Ibrutinib monotherapy lead-in of 3 cycles
干预措施: Venetoclax (Biological)
结局指标
主要结局
Investigator-assessed progression-free survival (PFS)
时间窗: Up to 80 month
Time from randomization to the first occurrence of progression or relapse (determined using standard iwCLL guidelines), or death from any cause, whichever occurs first
次要结局
- Rates of undetectable minimal residual disease (uMRD) in peripheral blood (PB) and bone marrow (BM)(At final restaging (RE): 18 months after start of treatment and additional BM assessment approx. 12 months after RE)
- MRD levels in PB at different time points(Up to 80 month)
- Overall response rate (ORR)(At final restaging (RE): 18 months after start of treatment)
- CR/CRi rate(At final restaging (RE): 18 months after start of treatment)
- Event-free survival(Up to 80 month)
- Time to next treatment(Up to 80 month)
- PFS2(Up to 80 month)
- Incidence of safety parameters such as adverse events (AE) and adverse events of particular/special interest (AEPI/AESI)(Up to 80 month)
- Safety parameter TLS(Up to 80 month)
研究者
研究点 (180)
Loading locations...
相似试验
已完成
3 期
A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic LeukemiaRelapsed or Refractory Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaNCT01578707Pharmacyclics LLC.391
已完成
3 期
Study of Ibrutinib and Rituximab in Treatment Naïve Follicular LymphomaFollicular LymphomaNCT02947347Pharmacyclics LLC.445
Unknown
2 期
Protocol GELLC-7: Ibrutinib Followed by Ibrutinib Consolidation in Combination With OfatumumabChronic Lymphocytic LeukemiaNCT03280160PETHEMA Foundation84
招募中
2 期
Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLLChronic Lymphocytic LeukemiaNCT04908228Paolo Ghia53
招募中
1 期
Multi-cohort Study to Customize Ibrutinib Treatment Regimens for Patients with Previously Untreated Chronic Lymphocytic Leukemia TAILORntreated Chronic Lymphocytic LeukemiaMedDRA version: 21.1Level: PTClassification code: 10003908Term: B-cell small lymphocytic lymphoma Class: 100000004864MedDRA version: 21.1Level: PTClassification code: 10008958Term: Chronic lymphocytic leukaemia Class: 100000004864CTIS2023-504044-34-00Janssen - Cilag International336
相关资讯
AbbVie Presents Breakthrough Data at ASH 2025 Demonstrating Significant Advances in Blood Cancer Treatment- AbbVie unveiled compelling clinical data at ASH 2025 showcasing advances across multiple blood cancer therapeutic modalities including T-cell engagers, BCL-2 inhibitors, and antibody-drug conjugates.
- The phase 3 EPCORE FL-1 trial demonstrated that epcoritamab plus rituximab and lenalidomide reduced disease progression risk by 79% in relapsed/refractory follicular lymphoma patients.
- Investigational therapies etentamig and PVEK showed promising efficacy with 81% overall response rates in multiple myeloma and 63.3% complete response rates in acute myeloid leukemia, respectively.9 months agoEvolving Strategies in CLL: Rethinking Continuous BTK Inhibitor Therapy- Emerging data suggest that continuous BTK inhibitor therapy in CLL may not always be necessary, challenging traditional treatment approaches.
- Combinations of BTK inhibitors with BCL-2 inhibitors show promise in achieving deep responses and treatment-free remission in CLL patients.
- Ongoing trials are investigating BCL2 inhibitor–free, fixed-duration regimens, exploring the potential of time-limited BTK inhibitor plus mAb therapies.
- Factors like disease genetics, prior treatment, and response depth should guide decisions on stopping BTK inhibitor therapy, alongside patient preferences and tolerance.last year