2025-521666-10-01招募中2 期
PirtobrUtinib as frontline Therapy for elderly unfit/frail patient with MAntle cell lymphoma: a phase II study of the Fondazione Italiana Linfomi (FIL)
Fondazione Italiana Linfomi Ets20 个研究点 分布在 1 个国家目标入组 56 人开始时间: 2026年2月26日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 56
- 试验地点
- 20
- 主要终点
- PFS defined as the time between the start of treatment and the first documentation of recurrence, progression or death for any cause
研究概览
简要总结
To evaluate the efficacy, in terms of 12-month Progression Free Survival (1yr-PFS), of a treatment with Pirtobrutinib monotherapy in untreated elderly unfit/frail MCL patients
入排标准
- 年龄范围
- 65 years 至 65+ years（65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Histologically documented diagnosis of nodal and extranodal mantle cell lymphoma (MCL) as defined in the 2022 edition of the World Health Organization (WHO) classification (For details refer to specific section in protocol)
- •The patient must give written informed consent
- •Male subjects must use highly effective contraception during sexual contact with a pregnant female or a female of childbearing potential from the start of study treatment and continuing for at least 3 months after the last dose of pirtobrutinib
- •Availability of biopsy material for central pathology revision and mutational analysis including TP53 mutations
- •Age ≥ 70 years
- •Previously untreated MCL
- •Active disease in need of treatment according to clinical practice (patients with leukemic with syntomatic leukemic non nodal disease may be included)
- •Ineligible to standard full-dose induction therapy (i.e. BR, R-CHOP, VR-CAP, RBAC500)
- •sGA assessment performed before starting treatment (Appendix H) FRAIL patients defined as follows: − Age ≥ 80 years − ADL <6 residual functions and/or − IADL <8 residual functions and/or − CIRS: ≥ 1 comorbidity of grade 3-4 or ≥ 5 comorbidities of grade 2; UNFIT patients defined as follows: − Age ≥ 80 years: − ADL 6 residual functions and − IADL 8 residual functions and − CIRS 0 comorbidities of grade 3-4 and <5 comorbidities of grade 2; or − Age < 80 years: − ADL < 5 residual functions and/or − IADL < 6 residual functions and/or − CIRS ≥ 1 comorbidity of grade 3-4 or >8 comorbidities of grade 2
- •Ann Arbor Stage I - IV (Appendix A)
- •At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
- •ECOG performance status of 0- 2 (Appendix C)
- •Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows: a. Hemoglobin ≥ 8 g/dL (independent of transfusions within 7 days of screening assessment) b. White blood cells (WBC) > 2500/mmc with polymorphonuclear (cells) PMN≥750/ mmc) (independent of growth factor support within 7 days of screening assessment) c. Platelets count ≥ 50000/mmc (independent of transfusions within 7 days of screening assessment)
- •Adequate renal function: − Creatinine clearance ≥ 30 mL/min (Appendix B) or − Serum creatinine ≤ 2.5 mg /dL
- •Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x ULN
- •Adequate hepatic function: − ALT or AST ≤ 3 x the ULN or ≤ 5 x ULN with documented liver involvement; − Total bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN with documented liver involvement and/or due to Gilbert’s Disease
- •Ability and willingness to comply with the study protocol procedure
- •Life expectancy > 6 months
- •The patient is able to take oral medications
排除标准
- •Candidate to watch and wait due to indolent presentation
- •History of severe bleeding diathesis (major bleeding event) NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2 g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome)
- •Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir
- •FIT patients according to sGA eligible to standard full dose therapy
- •Leukemic non-nodal MCL that has stable asymptomatic disease should not be included in this study
- •Histological diagnosis different from MCL or leukemic non-nodal MCL
- •Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrollment to maintain adequate blood counts
- •Significant cardiovascular disease defined as: a) unstable angina or acute coronary syndrome within the past 2 months prior to study enrollment b) history of myocardial infarction within 3 months prior to study enrollment or c) documented left ventricular ejection fraction (LVEF) by any method of ≤ 40% in the 12 months prior to study enrollment d) ≥ Grade 3 NYHA functional classification system of heart failure e) Uncontrolled or symptomatic arrhythmias
- •Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia’s Formula (QTcF): QTcF = QT/(RR0.33): a) Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator’s discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation. b) Correction for underlying bundle branch block (BBB) allowed. Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
- •Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
- •Candidate or eligible to full-dose BR, R-CHOP, VR-CAP, RBAC500 or any other full dose intensive chemotherapy
- •Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, HCV-RNA is required. Only patients with HCV-RNA negative are accepted.
- •Suspect or clinical evidence of CNS involvement by lymphoma
- •Contraindication to the use BTKi
- •HBsAg positivity; HBsAg-negative patients with anti-HBc antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and prophylactic antiviral treatment is provided
- •History of stroke or intracranial hemorrhage within 6 months of investigation treatment
- •History of CAR-T within 60 days of investigation treatment or presence of any of the following, regardless of prior SCT and/or CAR-T therapy timing: a) active graft versus host disease (GVHD); b) cytopenia from incomplete blood cell count recovery post-transplant; c) need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy; d) ongoing immunosuppressive therapy (> 20 mg prednisone or equivalent daily)
- •Evidence of any severe active acute or chronic infection
- •Absence of caregivers in non-autonomous patients
- •Need of anticoagulation with warfarin or another vitamin K antagonist
- •Vaccination with live vaccine within 28 days prior to investigation treatment
- •Have a known hypersensitivity to any of the excipients of Pirtobrutinib or to any intended study medications
- •Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible
- •HIV positivity
- •Clinically significant active malabsorption syndrome or other conditions likely to affect gastrointestinal (GI) absorption of the study drug
- •Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and medical monitor may pose a risk for patient participation. Screening for chronic conditions is not required
- •Major surgery within 4 weeks prior to investigation treatment
- •Any history of other malignancies unless in remission and with life expectancy > 2 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
- •Patients who experienced grade ≥ 3 arrhythmia.
结局指标
主要结局
PFS defined as the time between the start of treatment and the first documentation of recurrence, progression or death for any cause
PFS defined as the time between the start of treatment and the first documentation of recurrence, progression or death for any cause
次要结局
- Overall response rate [ORR = complete response (CR) + partial response (PR) rate) (according to Lugano, 2014 criteria)]
- Complete response rate (CRR)
- Overall survival (OS) defined as the time between the start of treatment and death from any cause
- Event free survival (EFS) defined as the time between the start of treatment and treatment failure including disease progression, or discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death)
- Duration of response (DOR) defined as the time from the first documentation of tumor response to disease progression or death from any cause
- Drop-out rate
- Rate of treatment discontinuation due to AE or treatment intolerance
- Frequency and severity of AEs and SAEs classified as per latest version of CTCAE
- The health-related quality of life (HRQoL) as measured by the EuroQol 5-Dimension Scale (EQ-5D-5L) and the Functional Assessment of Cancer Therapy for Patients with Lymphoma (FACTLym) standardized questionnaire on health status
研究者
Prof. Carlo Visco
Scientific
Fondazione Italiana Linfomi Ets
研究点 (20)
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