NCT06186648招募中2 期
A Phase 2 Study Evaluating the Bispecific CD3xCD20 Antibody GLOfitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) in Patients With RIchter Syndrome as Frontline therapY. A FILO Study
French Innovative Leukemia Organisation38 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2024年3月21日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 38
- 主要终点
- Objective response regarding Richter Syndrome to R/G-CHOP + glofitamab combination.
研究概览
简要总结
This is a national clinical trial, multicentric (28 centers), non-randomized phase 2 study.
Population: Patients with previously untreated Richter's syndrome (RS), defined as the occurrence of an aggressive lymphoma (of diffuse large B-cell lymphoma histology) in a patient with chronic lymphocytic leukemia (CLL).
Study treatment:
The duration of each cycle is 21 days.
Cycle 1:
Participants will receive standard of care doses of R-CHOP in cycle 1 as follows:
- Rituximab 375 mg/m² IV Day 1
- Cyclophosphamide 750 mg/m² IV Day 1
- Doxorubicin 50 mg/m² IV Day 1
- Vincristine 1.4 mg/m² [capped at 2.0 mg] IV Day 1
- Prednisone 60 mg/m2 per day PO Day 1-5
Cycle 2:
In order to minimize cytokine release syndrome (CRS), participants will then receive G-CHOP as cycle 2 (with obinutuzumab) and glofitamab:
- Obinutuzumab 1000 mg single dose IV Day 1
- Cyclophosphamide 750 mg/m² IV Day 1
- Doxorubicin 50 mg/m² IV Day 1
- Vincristine 1.4 mg/m² [capped at 2.0 mg] IV Day 1
- Prednisone 60 mg/m2 per day PO Day 1-5
- Glofitamab : administered intravenously (IV) as a step-up dose on Days 8 (2.5 mg) and 15 (10 mg)
Cycle 3-6:
Participants will receive standard of care doses of R-CHOP and Glofitamab as follows:
- Rituximab 375 mg/m² IV Day 1
- Cyclophosphamide 750 mg/m² IV Day 1
- Doxorubicin 50 mg/m² IV Day 1
- Vincristine 1.4 mg/m² [capped at 2.0 mg] IV Day 1
- Prednisone 60 mg/m2 per day PO Day 1-5
- Glofitamab : 30 mg IV Day 8
Cycle 7 and 8 (only for patient in Complete Response or Partial response after Cycle 6):
Cycle 7 and 8 consist of 2 infusions of glofitamab only at D8C7 and D8C8:
● Glofitamab : 30 mg IV Day 8
Primary endpoint Percentage of participants with a complete response as assessed by the investigator using the Cheson IWG 2014 Lugano Classification (i.e. Deauville scale 1-3) after 6 cycles of R/G-CHOP + glofitamab or at permanent treatment discontinuation.
End of treatment is defined as after 6 cycles of R/G-CHOP + glofitamab. Permanent treatment discontinuation is defined as the discontinuation of all treatments (R/G-CHOP, glofitamab).
详细描述
Study design :
Open label, multicenter phase 2 trial
Population:
Patients with previously untreated Richter's syndrome (RS), defined as the occurrence of an aggressive lymphoma (of diffuse large B-cell lymphoma histology) in a patient with chronic lymphocytic leukemia (CLL).
Primary objective:
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma according to the revised iwCLL criteria with biopsy proven transformation to CD20 positive diffuse large B-cell lymphoma, consistent with RS according to the 2016 WHO classification
- •A fresh or archival tissue biopsy is mandatory
- •Previous therapy for CLL is allowed (but no prior therapy for RS)
- •Age greater than or equal to 18 years and less or equal to 80 years
- •ECOG performance status 0-2
- •Participants must have at least one measurable target lesion (≥ 1.5 cm) in its largest dimension by computed tomography (CT) scan. Measurable disease, defined as at least one bi-dimensionally measurable nodal or tumor lesion, defined as > 1.5 cm in its longest dimension or PET-CT with at least one hypermetabolic lesion. Patients without measurable disease but with proven bone marrow infiltration by the RS are eligible.
- •Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of either CLL or RS cells confirmed on biopsy: absolute neutrophil count ≥ 1.5 G/L, hemoglobin >10 g/dL, and platelet count ≥75 G/L independent of transfusion within 7 days of screening
- •Subject must have adequate coagulation tests: Prothrombin Time > 50%, Fibrinogen > 1 g/L
- •Adequate liver function: Total bilirubin ≤ 1.5 x ULN; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN
- •Adequate left ventricular ejection function (> 50 %)
- •Adequate renal function: creatinine clearance calculated by MDRD/Cockcroft-Gault formula of ≥ 40 mL/min
- •Negative serologic or PCR test results for acute or chronic HBV infection
- •Negative test results for HCV and HIV (Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation)
- •Prior vaccination to the SARS-Cov-2 virus and and SARS-CoV-2 PCR testing and negative result before study treatment administration at each treatment cycle
- •Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential. Patients must agree to either remain completely abstinent or to use two effective contraceptive methods* until:
- •If the patient is a male: at least 3 months after pre-treatment with obinutuzumab or RCHOP or 2 months after the last dose of glofitamab, whichever is longer. Men must refrain from donating sperm during this same period
- •If patient is a female of childbearing potential: until at least 18 months after pre-treatment with obinutuzumab or RCHOP or 2 months after the last dose of glofitamab, whichever is longer
- •Ability to understand and the willingness to sign a written informed consent document. Patient must be willing and able to comply with protocol-mandated hospitalization upon administration of the first dose of glofitamab. Patient must also be willing to comply with all study-related procedures
- •Signed written informed consent
- •Patient covered by any social security system
排除标准
- •Patients with the Hodgkin variant of RS
- •Patients with previously treated for RS
- •Current or past history or presence of clinically relevant disorder affecting the central nervous system (CNS)
- •Ineligible to CHOP full dose for any reason
- •Previous treatment with a bispecific antibody
- •Current or past history of DLBCL in the CNS (confirmed by CSF analysis)
- •Steroids treatment (> 1 mg/kg/d for one week) before inclusion
- •History of anaphylactic reactions to human, chimeric, or mouse monoclonal antibodies or to any components of the product.
- •Prior allogeneic HSCT
- •Patients with known acute infection or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, HIV and SARS-CoV-2), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks prior to the first study treatment.
- •History of other malignancies, except: i) malignancy treated with curative intent and with no recurrence over the last 3 years ii) adequately treated non-melanoma skin cancer without evidence of disease iii) adequately treated carcinoma in situ without evidence of disease
- •Prior solid organ transplantation
- •History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
- •Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy
- •Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation
- •Current uncontrolled autoimmune disease*
- •History of human immunodeficiency virus
- •Hepatitis B or C seropositivity (unless clearly due to vaccination)
- •Pregnant or breastfeeding women
- •Unwilling or unable to participate in all required study evaluations and procedures.
- •Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form and authorization to use protected health information (in accordance with national and local subject privacy regulations)
- •Persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure (guardianship, curatorship, legal protection), persons under psychiatric care
- •Fertile male patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study.
- •Patients with history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH)
- •LVEF < 50% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan, significant or extensive cardiovascular disease such as New York HeartAssociation Class III or IV cardiac disease or Objective Assessment Class C or D,myocardial infarction within the last 3 months, unstable arrhythmias, or unstable angina.
- •Abnormal screening laboratory values as defined as following: a) ALT (SGOT) and/or ALT (SGPT) and/or ALP ≥ 3 x upper limit of normal (ULN); b) Total bilirubin ≥ 1.5 x ULN, unless due to Gilbert's disease; c) Creatinine ≥ 2.0 x ULN or creatinine clearance < 40 mL/min (calculated).
- •Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- •Major surgery or significant traumatic injury < 28 days prior to the obinutuzumab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- •Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion
- •Treatment with another investigational agent or participating in another trial within 30 days prior to entering the study
- •Clinically significant history of liver disease or cirrhosis
- •Pregnant or breast-feeding or intending to become pregnant during the study
- •No affiliation to social security
- •Inability to comply with protocol mandated hospitalization and restrictions.
研究组 & 干预措施
Glofitamab + Obinutuzumab
Experimental
cf Intervention
干预措施: Glofitamab + Obinutuzumab (Drug)
结局指标
主要结局
Objective response regarding Richter Syndrome to R/G-CHOP + glofitamab combination.
时间窗: 6 cycles (each cycle is 21 days)
Percentage of patients with a complete response (CR) assessed using the Cheson IWG 2014 Lugano Classification (i.e. Deauville scale 1-3)
次要结局
- Safety and toxicity of the R/G-CHOP + glofitamab combination(Through treatment completion, an average of 8 months)
研究者
研究点 (38)
Loading locations...
相似试验
进行中（未招募）
3 期
A Trial of SHR1701 Plus Chemotherapy in Patients With Gastric or Gastroesophageal CancerGastric or Gastroesophageal Junction CancerNCT04950322Suzhou Suncadia Biopharmaceuticals Co., Ltd.737
招募中
2 期
Docetaxel, Oxaliplatin and 5-FU for Gastric Cancer With Inoperable Malignant Bowel ObstructionMetastatic Gastric AdenocarcinomaMetastatic Gastroesophageal Junction AdenocarcinomaPeritoneal CarcinomatosisNCT04840264Sixth Affiliated Hospital, Sun Yat-sen University79
已完成
3 期
Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) InhibitorsArthritis, RheumatoidNCT04134728GlaxoSmithKline550
招募中
2 期
A Clinical Study to Evaluate Efficacy and Safety of Serplulimab（HLX10） Combined With Bevacizumab（HLX04) and Chemotherapy (XELOX) in Patients With Metastatic Colorectal Cancer (mCRC)Metastatic Colorectal CancerNCT04547166Shanghai Henlius Biotech568
进行中（未招募）
2 期
Evaluation of MN-166 (Ibudilast) for 12 Months Followed by an Open-label Extension for 6 Months in Patients With ALSAmyotrophic Lateral SclerosisNCT04057898MediciNova234