2022-501187-18-00招募中3 期
A Randomized, Open-label, Phase 3 Study of Acalabrutinib in Combination with Rituximab and Reduced Dose CHOP (R-miniCHOP) in Older Adults with Untreated Diffuse Large B-Cell Lymphoma (ARCHED/GLA 2022-1)
University Of Saarland55 个研究点 分布在 2 个国家目标入组 330 人开始时间: 2023年4月3日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 330
- 试验地点
- 55
- 主要终点
- PFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Disease progression (PD), relapse after complete remission (CR) or death due to any cause, as per Lugano Classification of 2014. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of adequate disease assessment (for definition see 10.6.1)..
研究概览
简要总结
To evaluate if the addition of acalabrutinib to R-miniCHOP prolongs progression-free survival (PFS), compared to R-miniCHOP alone in patients >80 years or >60 years and ineligible for full-dose R-CHOP with previously untreated DLBCL, based on investigator-assessed response.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Ability to understand the purpose and risks of the study and capable of giving signed informed consent which includes: a. Compliance with the requirements and restrictions listed in the informed consent form (ICF). b. Authorization to use protected health information/data [in accordance with the General Data Protection Regulation (GDPR)].
- •Meet the following laboratory parameters: a. Absolut neutrophil count (ANC) ≥ 1500 cells/µl or platelet count ≥ 100.000/µl unless directly attributable to lymphoma. b. Serum AST and ALT ≤3 x upper limit of normal (ULN) unless directly attributable to lymphoma. c. Total bilirubin ≤1.5 x ULN, unless directly attributable to Gilbert’s syndrome or lymphoma. d. Estimated creatinine clearance of ≥30 mL/min, calculated by Cockcroft-Gault (using actual body weight) (if male, [140-Age] x Mass [kg] / [72 x serum creatinine mg/dL]; multiply by 0.85 if female), or serum creatinine ≤2.5 x ULN.
- •Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
- •Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
- •Men and women >80 years of age or >60 up to 80 years of age and ineligible for full dose R-CHOP according to investigator assessment after standardized geriatric assessment
- •Male patients who are sexually active with women of childbearing potential (definitions see section 17.8 of the protocol) must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study (see section 17.8.1 of the protocol) as well as to the restrictions mentioned in section 9.13 of the protocol
- •Female patients of childbearing potential (definitions see 17.8 in the protocol) who are sexually active must agree to use highly effective forms of contraception while on the study as well as to the restrictions mentioned in section 9.
- •of the protocol
- •Histologically proven, previously untreated CD20+ diffuse large B-cell lymphoma (DLBCL) according to the 2017 WHO classification including: a. diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) b. primary cutaneous DLBCL leg type c. intravascular large B-cell lymphoma d. EBV+ DLBCL, NOS e. HHV8+DLBCL, NOS f. primary mediastinal (thymic) large B-cell lymphoma g. B-cell lymphoma, with intermediate features between DLBCL and classical Hodgkin lymphoma h. follicular lymphoma grade 3B i. high-grade B-cell lymphoma, NOS j. high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements k. T-cell/histiocyte-rich large B-cell lymphoma l. DLBCL associated with chronic inflammation m. ALK+ large B-cell lymphoma n. large B-cell lymphoma with IRF4 rearrangement Please note: patients in whom indolent lymphoma is diagnosed concurrently with the one of the above listed diagnoses can also be included
- •Disease Stage I with bulk ≥7.5cm, II, III or IV according to Ann Arbor Classification
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •An ECOG Score of 3 is acceptable only if this is directly attributable to lymphoma
排除标准
- •Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator’s opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol [e.g. a single score of 4 on one single category on the CIRS-G-Score (but not a cumulative score of 4)].
- •Concurrent participation in another therapeutic clinical trial.
- •Any active significant infection (e.g., bacterial, viral or fungal) as assessed by the investigator.
- •Severe pulmonary dysfunction (CTCAE grade 3 or 4) unless associated with lymphoma.
- •Severe psychiatric or neurologic disease that, in the investigator’s opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
- •Persistent neuropathy CTCAE grade 3 or 4
- •Refractory nausea and vomiting, inability to swallow acalabrutinib, or malabsorption syndrome; chronic severe gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment.
- •History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following: a. Curatively treated localised basal cell carcinoma or localised squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ / low risk carcinoma of the prostate requiring only observation, as well as untreated low grade lymphoma except chronic lymphocytic leukemia. b. Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥2 years (≥5 years for those treated with chemotherapy) without further treatment or which are not expected to limit survival to < 2 years.
- •Received a live virus vaccination within 28 days of randomization.
- •Known history of infection with HIV.
- •History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
- •Diagnosis of primary central nervous system lymphoma or secondary central nervous system or meningeal involvement by lymphoma
- •Serologic status reflecting active hepatitis B or C infection. a. Patients who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before randomization and must be willing to undergo DNA PCR testing during the study. Those who are HBsAg-positive or hepatitis B PCR positive will be excluded. b. Patients who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.
- •History of stroke or intracranial hemorrhage within 6 months before randomization
- •History of clinically relevant bleeding diathesis (e.g., hemophilia, von Willebrand disease).
- •Major surgical procedure within 30 days before randomization. Note: If a patient had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- •Breastfeeding or pregnant women
- •Current life-threatening illness, medical condition, organ system dysfunction, social, geographical or economic condition which, in the Investigator’s opinion, could compromise the patient’s safety or put the study at risk.
- •Diagnosis of Richter’s Transformation/transformed CLL
- •Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of randomization or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or LVEF < 40%. Patients with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
- •Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists. Patients using therapeutic low molecule weight heparin, direct oral anticoagulants or low dose aspirin will be eligible. Switching from vitamin K antagonists to one of the allowed anticoagulants above prior to trial entry is permitted.
- •Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor or inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited. See details in section 9.12.1 of the protocol
- •Prior exposure to a BTK inhibitor.
- •Prior anthracycline use >300 mg/m2 of doxorubicin equivalent.
- •Already initiated lymphoma therapy except for steroid (max. total dose of 1500mg of prednisolone equivalent), vincristine (max. 1 mg once) and/or rituximab (max. total dose of 375mg/m2) prephase.
结局指标
主要结局
PFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Disease progression (PD), relapse after complete remission (CR) or death due to any cause, as per Lugano Classification of 2014. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of adequate disease assessment (for definition see 10.6.1)..
PFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Disease progression (PD), relapse after complete remission (CR) or death due to any cause, as per Lugano Classification of 2014. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of adequate disease assessment (for definition see 10.6.1)..
次要结局
- PFS, as defined above, based on blinded independent central review (BICR).
- OS, defined by the time between the day of randomization until death due to any cause. Patients who have not experienced an event at the time of analysis will be censored at the date when the patient was last known to be alive.
- EFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Progressive disease (PD), relapse after complete remission (CR), initiation of subsequent systemic anti-lymphoma treatment and/or irradiation or death due to any cause, as per Lugano Classification of 2014. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of adequate disease assessment.
- PFS, OS and EFS, as defined above, according to cell of origin (COO) as per immunohistochemistry and gene expression analysis
- PFS, OS and EFS, as defined above according to DLBCL molecular genotype.
- PFS, OS and EFS, as defined above, according to age groups (>60 - 80 years vs >80 years) and according to gender and serum albumin.
- Rate of (metabolic) CR, defined as the number of patients achieving CR as best overall response after end of study treatment divided by the number of randomized patients.
- Rate of PR, defined as the number of partial remissions after end of study treatment divided by the number of randomized patients.
- Overall response rate (ORR), defined as the number of complete and partial remissions after end of study treatment, divided by the number of randomized patients.
- Duration of response (DoR), defined as the time from documentation of tumor response to disease progression or relapse, or death of any cause.
- Progression rate, defined as the number of progressions after end of study treatment divided by the number of randomized patients.
- Relapse rate, defined as the number of relapses divided by the number of patients with complete remission after end of study treatment.
- CNS relapse rate, defined as the cumulative CNS incidence rate.
- AEs, SAEs, adverse events of special interest (AESIs), events of clinical interest, AEs leading to study treatment discontinuation or dose modification. Rate of secondary malignancies, defined as the number of patients with secondary malignancies divided by the number of randomized patients.
- Treatment-related death rate, defined as the number of treatment related deaths during therapy or up to 2 months after the end of study treatment, but before the start of further treatment, divided by the number of randomized patients.
- Number and duration of therapy cycles, cumulative and relative doses of miniCHOP, rituximab and acalabrutinib.
研究者
Central Trial Office
Scientific
University Of Saarland
研究点 (55)
Loading locations...
相似试验
招募中
2 期
Orelabrutinib Plus Lisaftoclax and Rituximab in Untreated Mantle Cell Lymphoma With High-Risk DiseaseNCT07272499Ruijin Hospital25
尚未招募
2 期
PreVent-ACaLLChronic Lymphocytic Leukemia2024-511072-33-00Rigshospitalet50
招募中
3 期
A Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.2025-522860-34-00BeOne Medicines AG196
招募中
3 期
Phase III randomized clinical trial evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer considering two different settings: Primary Debulking Surgery (PDS) and Interval Debulking Surgery (IDS)2024-514706-31-01Centre Oscar Lambret352
尚未招募
3 期
Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy after Induction Treatment for Hormone Receptor Positive (HR+)/HER2-Positive Metastatic Breast CancerBreast Cancer2024-513540-29-00Alliance Foundation Trials LLC303