2023-508259-38-00招募中3 期
An open-label, prospective Phase III clinical study to compare polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) with rituximab, ifosfamide, carboplatin and etoposide (R-ICE) alone as salvage therapy in patients with primary refractory or relapsed diffuse large B-cell lymphoma (DLBCL)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- GWT-Tud GmbH
- 入组人数
- 302
- 试验地点
- 47
- 主要终点
- The primary endpoint is EFS of patients with DLBCL at first progression or relapse.
研究概览
简要总结
The primary objective of this study is to investigate the following question in patients with relapsed or primary refractory DLBCL: Does salvage therapy with Pola-R-ICE improve event-free survival (EFS) compared to R-ICE alone?
研究设计
- 分配方式
- Randomized
- 主要目的
- Treatment phase
- 盲法
- None
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
- 是
入选标准
- •The informed consent form must be signed before any study specific tests or procedures are done
- •Adequate hematological function, as defined by: hemoglobin ≥ 8 g/dL, if anemia is attributable to underlying disease and transfusions result to an increase ≥ 8 g/dL, patients can be included, absolute neutrophil count (ANC) ≥ 1.0 x 109/L OR ≥ 0.5 x 109/L if neutropenia is attributable to underlying disease and before the administration of steroids, and platelet count ≥ 75 x 109/L OR ≥ 50 x 109/L if thrombocytopenia is attributable to underlying disease
- •Women of childbearing potential must have a negative pregnancy test result within 7 days prior to the first study drug administration
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
- •Adult male and female patients ≥18 years (≥16 years in the UK*) at the time of inclusion in the study * In the UK an “adult” means a person who has attained the age of 16 years, according to The Medicines for Human Use (Clinical Trials) Regulations 2004, Part 1 Point 2
- •Ability to understand and follow study-related instructions
- •Risk group: All patients with one of the following histologically defined entities: Histological diagnosis of primary refractory or relapsed aggressive B-cell non-Hodgkin lymphoma (B-NHL), confirmed by a biopsy of involved nodal or extranodal site. Patients with any of the following histologies can be included: • DLBCL not otherwise specified (NOS) • T-cell/histiocyte-rich large B-cell lymphoma • Primary cutaneous DLBCL, leg type • Epstein-Barr virus (EBV)-positive DLBCL, NOS • DLBCL associated with chronic inflammation • Primary mediastinal (thymic) large B-cell lymphoma • High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements • High-grade B-cell lymphoma, NOS
- •Performance Status ECOG 0-2 at time of randomization or ECOG 3 at screening if this is DLBCL-related and has improved to ECOG 2 or less with a 7-day steroid treatment during the screening phase (e.g. 1 mg/kg prednisone)
- •Information on all 5 International Prognostic Index (IPI) factors
- •Staging (PET-CT based-staging according to Lugano criteria 2014). Patients must have PET-positive lesions
- •Subjects must have received adequate first line therapy including at a minimum: i) anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and ii) an anthracycline containing chemotherapy regimen
- •Intent to proceed to high-dose therapy (HDT) and stem cell transplantation (SCT) if response to second line therapy
排除标准
- •Serious accompanying disorder leading to impaired organ function causing significant clinical problems and reduced life expectancy of less than 3 months. In particular, patients with the following organ dysfunction caused by accompanying disorders are to be excluded: • Heart failure with left ventricular ejection fraction (LVEF) < 45% • Impaired pulmonary function with vital capacity (VC) or forced expiratory volume (FEV1) < 50% of normal (only in case of history of significant pulmonary disease) • Impaired renal function with glomerular filtration rate (GFR) < 50 mL/min (calculated) • Impaired liver function with alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) or bilirubin > 1.5 x upper limit of normal (ULN). If elevation is caused by the disease, threshold of 2.5 x ULN is accepted • Peripheral neuropathy > Grade II
- •Patients with suspected or latent tuberculosis. Latent tuberculosis needs to be confirmed by positive interferon-gamma release assay
- •Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment
- •Richter’s transformation or prior chronic lymphocytic leukemia (CLL)
- •Vaccination with a live vaccine within 4 weeks prior to treatment
- •Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis
- •History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
- •History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure
- •Contraindications according to the Investigator´s Brochure (IB) of polatuzumab vedotin or the local Summary of Product Characteristics (SmPCs) of the used rituximab, ifosfamide, carboplatin or etoposide products
- •Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject’s safety
- •Pregnancy or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug
- •Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1
- •Close affiliation with the investigator (e.g. a close relative) or persons working at the study site
- •Subject is an employee of the sponsor or involved Contract Research Organization
- •Received more than one line of therapy for DLBCL
- •Received polatuzumab vedotin as part of the first line therapy
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- •Ongoing treatment or study procedures within any other Investigational Medicinal Product (IMP) clinical trial with the exception of follow-up. In case of a preceding clinical trial, last application of the respective IMP(s) must have been done more than five elimination half-lives before start of study medication in this trial
- •Human immunodeficiency virus (HIV)-positivity with detectable viral load and/or a CD4+ count below 0.3/nL
- •Hepatitis B and C are defined by seropositivity (HBsAg and anti HBc; anti-HCV). Patients with occult or prior HBV infection (defined as negative HBsAg and positive hepatitis B core antibody [Anti-HBc]) or HCV infection (defined as undetectable HCV RNA and positive anti-HCV) may be included if HBV DNA or HCV RNA is undetectable, provided that they are willing to undergo DNA testing on Day 1 of every cycle and monthly for at least 12 months after the last cycle of study treatment. In case of false positive serology (transfused antibodies) negative PCR-results will allow patient inclusion
- •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study inclusion or any unresolved major episode of infection (as evaluated by the investigator) within 1 week prior to Cycle 1 Day 1
结局指标
主要结局
The primary endpoint is EFS of patients with DLBCL at first progression or relapse.
The primary endpoint is EFS of patients with DLBCL at first progression or relapse.
次要结局
- Secondary endpoints for efficacy are rate of metabolic CR after end of study treatment, PR rate, ORR, duration of response, progression rate, relapse rate, PFS, OS, number of CD34+ cells, mobilization failure rate, rate of patients proceeding to transplantation, and non-relapse mortality
- Secondary safety endpoints: Adverse events (AE), Serious adverse events (SAE), Incidence and duration of neutropenia and thrombocytopenia Grade 4 CTC, Rate of treatment-related deaths, Second malignancies
- Secondary endpoints for protocol adherence: Number of chemotherapy cycles, Duration of chemotherapy cycles, Cumulative dose and relative dose of ifosfamide, carboplatin and etoposide, Cumulative dose and relative dose of rituximab, Cumulative dose and relative dose of the polatuzumab vedotin
- Secondary endpoints for QoL: Secondary endpoint is evaluation of generic health-related QoL as assessed by different questionnaires
研究者
FB MEDIZIN
Scientific
GWT-Tud GmbH
研究点 (47)
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