NCT04161118终止2 期
Phase II Trial of TisaGenlecleucel in Elderly Patients With First-Relapsed or Primary Refractory Aggressive B-cell Non-Hodgkin Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Estimation of the efficacy of treatment with tisagenlecleucel (CTL019) in elderly patients with r/r aNHL by measuring the complete metabolic response (CMR) rate 12 weeks after tisagenlecleucel (CTL019) infusion
研究概览
简要总结
A phase II trial of TisaGenlecleucel (CTL019) in Elderly Patients with First-Relapsed or Primary Refractory Aggressive B-cell Non-Hodgkin Lymphoma
详细描述
This is a single-arm, prospective, multicenter phase-II trial for elderly patients with aNHL failing 1st-line treatment with immunochemotherapy containing rituximab and anthracycline, who are not eligible for either autologous or allogeneic stem cell transplantation, defined as age > 65 years, or > 60 years old with HCT-CI score >2. This trial evaluates the CMR rate 12 weeks after tisagenlecleucel (CTL019) infusion, the incidence and severity of adverse events, progression-free survival, and overall survival after one and two years after tisagenlecleucel (CTL019).
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
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written, signed and dated informed consent must be obtained prior to participation in the study
- •Patients with first relapse of aggressive B-cell Non-Hodgkin Lymphoma (aNHL) within 365 days after rituximab- and anthracycline-containing first-line immunochemotherapy or aNHL refractory to first-line therapy (not achieving a CR or PR), who are ineligible for either autologous or allogeneic stem cell transplantation, defined by age > 65 years, or > 60 years with a HCT-CI score > 2 (https://qxmd.com/calculate/calculator_108/hematopoietic-cell-transplantation-specific-comorbidity-index-hct-ci) and not older than 80 years.
- •Histologically confirmed (by local histopathological assessment) aNHL at relapse or progression due to refractory disease after front line therapy. aNHL is defined by the following list of subtypes:
- •DLBCL, NOS (GCB, ABC, centroblastic, immunoblastic, anaplastic)
- •FL grade 3B
- •T-cell-rich/histiocyte-rich large B-cell lymphoma (T/HRBCL)
- •DLBCL associated with chronic inflammation
- •Intravascular large B-cell lymphoma
- •ALK+ large B-cell lymphoma
- •B-cell lymphoma, unclassifiable, (with features intermediate between DLBCL and classical HL)
- •High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
- •High-grade B-cell lymphoma, NOS
- •HHV8+ DLBCL, NOS
- •DLBCL transformed from follicular lymphoma
- •DLBCL transformed from marginal zone lymphoma
- •DLBCL, leg type
- •Measurable disease:
- •Nodal lesions >15 mm in the long axis, regardless of the length of the short axis, and/or
- •Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long AND short axis
- •ECOG performance status 0-2
- •Adequate organ function:
- •a. Kidney function defined as: i. Serum creatinine estimated glomerular filtration rate GFR ≥ 30mL/min b. Hepatic function defined as: i. ALT and AST ≤ 5 × ULN, except for aNHL-related functional impairment. ii. Bilirubin ≤2.0 mg/dl except for patients with Gilbert syndrome, who may be included if their total bilirubin is ≤3.0 × ULN and direct bilirubin ≤1.5 × ULN OR for aNHL-related functional impairment c. Adequate bone marrow function (regardless of transfusion) defined as: i. WBC ≥2500/µL ii. Absolute neutrophil count (ANC) >1000/µL iii. Platelets ≥50,000/µL iv. Hemoglobin >8.0 g/dl d. Minimum level of pulmonary function defined as: i. No or mild dyspnea (≤ Grade 1) ii. pulse oxygenation ≥ 91% on room air
- •Life expectancy of more than six months
- •Women have to be in menopausal or post-menopausal status or confirmed as not having potential on childbearing
- •Male participants with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods as described in the study protocol
排除标准
- •Patients with Richter's transformation, Burkitt lymphoma, or primary CNS lymphoma (PCNSL)
- •Prior treatment with anti-CD19 therapy, adoptive T-cell therapy, or any prior gene therapy product
- •Treatment with any lymphoma-directed second-line anticancer therapy prior to enrollment with the exception of intermittent steroid therapy. After enrollment, bridging therapy is permitted for disease control.
- •Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated (i.e. patient is asymptomatic) and local treatment was >4 weeks before enrollment
- •Prior allogeneic bone marrow transplantation (HSCT)
- •Active hepatitis B, hepatitis C, or hepatitis E infection
- •HIV-positive patients
- •Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
- •Any of the following cardiovascular conditions:
- •Unstable angina, myocardial infarction, coronary artery bypass graft (CABG), or stroke within 6 months prior to screening,
- •LVEF <45% as determined by ECHO at screening except for aNHL-related functional impairment,
- •NYHA functional class III or IV (Chavey et al. 2001) at screening,
- •Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II) and third degree AV block, unless adequately controlled by pacemaker implantation,
- •Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening or inability to determine the QTcF interval,
- •Risk factors for Torsades de Point (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia, or any of the following:
- •Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or
- •Concomitant medication(s) with a "Known Risk of Torsades de Point" per www.qtdrugs.org that cannot be discontinued or replaced by safe alternative medication.
- •Previous or concurrent malignancy with the following exceptions:
- •Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
- •In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated carcinoma in situ without evidence of of recurrence for at least 3 years prior to the study
- •A primary malignancy which has been completely resected and in complete remission for ≥ 3 years
- •Pregnant or nursing (lactating) women and women who are not confirmed to be menopausal/post-menopausal. Or women who are capable of giving birth.
- •Intolerance to the excipients of the tisagenlecleucel cell product
- •Active or history of inflammatory disorders or autoimmune disease that required systemic steroids or immunosuppressive medications, with exception of vitiligo or resolved childhood asthma
- •Active tuberculosis
- •Exposure to any investigational agent(s) within 4 weeks prior to study entry
- •Chemotherapy less than 2 weeks before leukapheresis
- •Simultaneous radiotherapy to tisagenlecleucel infusion (radiotherapy between leukapheresis and day -6 before tisagenlecleucel infusion is permitted)
- •Ongoing necessity for systemic corticosteroids >10mg daily prednisone equivalent. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
- •History of active primary immunodeficiency
- •Major surgery (defined as opening at least one body cavity) within 4 weeks prior to study entry
- •History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening CT scan
- •Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CTLA-4 antibodies, other immune checkpoint inhibitors
- •Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
- •Current treatment within another therapeutic clinical trial with experimental and not approved drugs and treatment combinations
- •Patient's lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly
- •Non-compliance, e.g. due to
- •Drug dependency or substance abuse that would interfere with cooperation with requirements of the trial
- •Refusal of blood products during treatment
- •Change of residence to abroad
- •any similar circumstances that appear to make protocol treatment or long-term follow-up impossible
- •Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator
- •Committal to an institution on judicial or official order
研究组 & 干预措施
Tisagenlecleucel (CTL019)
Experimental
All patients will receive a single target dose of 0.6 to 6.0 × 108 of autologous tisagenlecleucel (CTL019) transduced T-cells with a viability of at least 70% administered via IV infusion after optional bridging with chemo- or immunotherapy and lymphodepleting (LD) chemotherapy with cyclophosphamide and fludarabine.
干预措施: CTL019 (Drug)
结局指标
主要结局
Estimation of the efficacy of treatment with tisagenlecleucel (CTL019) in elderly patients with r/r aNHL by measuring the complete metabolic response (CMR) rate 12 weeks after tisagenlecleucel (CTL019) infusion
时间窗: 12 weeks after tisagenlecleucel (CTL019) infusion
Estimation of the efficacy of treatment with tisagenlecleucel (CTL019) in elderly patients with r/r aNHL by measuring the complete metabolic response (CMR) rate 12 weeks after tisagenlecleucel (CTL019) infusion
次要结局
- Incidence and severity of adverse events (AEs)(From study start to study end (44 months))
- Overall survival (OS) rates at 1 and 2 year(s)(Up to two years from study start)
- Progression-free survival (PFS) rates at 1 and 2 year(s)(Up to two years from study start)
研究者
Prof. Dr. Peter Borchmann
Trial Chairman
University of Cologne
研究点 (2)
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