2022-500439-35-00招募中3 期
A phase 3 multicentre, randomized, prospective, open-label trial of Ibrutinib monotherapy versus fixed-duration Venetoclax plus Obinutuzumab versus fixed-duration Venetoclax plus Ibrutinib in patients with previously untreated chronic lymphocytic leukaemia (CLL) - CLL17
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 841
- 试验地点
- 123
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
The primary objective of the study is to compare the efficacy of continuous ibrutinib monotherapy with fixed-duration venetoclax plus obinutuzumab and fixed-duration venetoclax plus ibrutinib by measuring progression-free survival (PFS) in patients with previously untreated CLL.
研究设计
- 分配方式
- Randomized
- 主要目的
- Follow up
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Documented CLL/ Small lymphocytic lymphoma (SLL) 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: a) Absolute neutrophil count ≥ 1.0 × 10E9/L, b) Platelet counts ≥ 30 × 10E9/L; in cases of thrombocytopenia clearly due to CLL (per the discretion of the investigator), platelet count should be ≥ 10 × 10E9/L , c) Total haemoglobin ≥ 8 g/dL (without transfusion support, unless anaemia is due to CLL)
- •GFR >30ml/min directly measured with 24hr urine collection or 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 month if persistently negative until 12 months after last treatment cycle), and for hepatitis C (anti-HCV-ab negative; in case of positive HCV antibody test, negative HCV-PCR is required).
- •Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.
排除标准
- •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).
- •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 a) surgically sterile or ≥ 2 years after the onset of menopause or b) 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.
- •Transformation of CLL (Richter transformation). When Richter transformation is suspected, PET-CT and/or biopsy should be performed to rule out transformation.
- •Legal incapacity.
- •Prisoners or subjects who are institutionalized by regulatory or court order.
- •Persons who are in dependence to the sponsor or an investigator.
- •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 or phenprocoumon (alternative anticoagulation is allowed (e.g. DOACs), but patients must be properly informed about the potential risk of bleeding under treatment with ibrutinib).
结局指标
主要结局
Progression-free survival (PFS)
Progression-free survival (PFS)
次要结局
- Rates of undetectable MRD (uMRD, i.e. <10E-4) in peripheral blood (PB) and bone marrow (BM) at final restaging (RE), which will be at cycle 18 after start of treatment, and additional BM assessment approx. 12 months after RE
- MRD levels in PB at different time points (cycle 1 before start of ther-apy, start of cycle 7, start of cycle 13 [end of VG treatment], start of cycle 16 [end of VI treatment], final restaging [cycle 18], afterwards every 6 months to end of study)
- Duration of undetectable MRD (uMRD)
- Overall survival (OS)
- Overall response rate (ORR; defined as rate of a response of CR, CRi, or PR) as per iwCLL guidelines at final restaging
- Complete response rate (CRR; defined as rate of a response of CR or CRi) at final restaging as per iwCLL guidelines
- Duration of response
- Event-free survival (EFS) (I vs VG and I vs VI)
- Time to next treatment (TTNT)
- PFS2 (i.e. PFS after second-line treatment)
研究者
Othman Al-Sawaf
Scientific
University Of Cologne
研究点 (123)
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