2024-511635-94-00招募中2 期
An Open Label, Phase 2 Study to Evaluate Activity and Safety of Daratumumab in combination with Bortezomib and Dexamethasone in patients with Relapsed or Refractory Plasmablastic lymphoma (DALYA trial)
Fondazione Italiana Linfomi Ets21 个研究点 分布在 1 个国家目标入组 28 人开始时间: 2025年1月8日最近更新:
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 28
- 试验地点
- 21
- 主要终点
- Overall Response Rate (ORR = Complete response, CR+ Partial response, PR) after induction cycle 1 (daratumumab alone), after induction cycles 3, 6 and 9 (end of induction, EOI); after maintenance cycles 12 and 15 (end of treatment, EOT). Response will be defined according to the Lugano 2014 criteria. The best response achieved per patient will be considered for analysis.
研究概览
简要总结
To evaluate the activity of daratumumab as single agent and in combination with bortezomib/dexamethasone in patients with relapsed or refractory Plasmablastic lymphoma (PBL), who are not eligible for autologous or allogeneic transplantation or experienced relapse after a prior autologous stem cell transplantation.
研究设计
- 研究类型
- Interventional
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
- •Histologically confirmed plasmablastic lymphoma according to WHO 2017, CD38-positive by immunohistochemistry (≥5% of positive cells) Local diagnosis of PBL and local CD38 assessment ≥5% will suffice for enrollment and start of treatment.
- •Subject must be able to adhere to the study visit schedule and other protocol requirements
- •Patients with plasmablastic lymphoma relapsed or refractory: - after at least one line of conventional-dose chemotherapy followed or not by autologous stem cell transplantation; - after at least one line of conventional-dose chemotherapy and not eligible for salvage autologous or allogeneic transplantation;
- •ECOG Performance Status ≤ 3;
- •Age ≥ 18 years;
- •Both HIV-negative and HIV-positive patients are eligible;
- •HIV infection responsive to ongoing cART (combination antiretroviral therapy);
- •At least one measurable disease lesion identifiable by imaging: - A nodal lesion must be at least 11 mm x 11 mm OR ≥ 16 mm in the greatest transverse diameter (regardless of short axis measurement). - An extranodal lesion must be at least 10 mm x 10 mm.
- •Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and 7 months (for women) o 4 months (for men) after last administration of bortezomib or 6 months after last daratumumab dose, regardless of sex. A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control method (failure rate of less than 1%) e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, and sexual abstinence. The use of condoms by male patients is required unless the female partner is permanently sterile. WOCBP must have two negative pregnancy tests as verified by the study doctor prior to starting study therapy and must agree to undergo monthly pregnancy testing during the course of the study and after end of study therapy if clinically indicated. This applies even if the subject practices complete abstinence from heterosexual contact.
- •Subject understands and voluntarily signs and dates an informed consent form approved by the National Ethics Committee (NEC), prior to the initiation of any screening or study-specific procedures
排除标准
- •Histologic diagnosis different from confirmed plasmablastic lymphoma according to WHO 2017 and/or CD38 expression < 5% of positive cells
- •Screening laboratory values (due to causes different than lymphoma): - Absolute neutrophil count (ANC) <1.0 x 109/L (unless secondary to documented marrow involvement by lymphoma) - Platelet count <75 x 109/L - Hemoglobin < 7.5 g/dL - Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) > 3.5 times the upper limit of normal (ULN) - Alkaline phosphatase > 3.5 times ULN - Bilirubin > 2 times x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin) - Serum Creatinine Clearance < 20 ml/min
- •Subject has clinically significant cardiac disease, including: - Myocardial infarction within 6 months before date of registration, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) - Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] current version Grade 2 or higher) or clinically significant ECG abnormalities. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) > 470 msec
- •Evidence of any other clinically significant uncontrolled condition(s)
- •Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent
- •Breastfeeding women or women with a positive pregnancy test at screening
- •CNS involvement
- •Patients with known hypersensitivity to the investigational drug or to product components or severe allergic or anaphylactic reactions to humanized products
- •Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy including targeted small molecule agents within 14 days prior to the first dose of study drug
- •Concomitant Kaposi sarcoma; however, patients with only skin involvement of KS can be included.
- •Subject is: - Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [HBcAb] ± antibodies to hepatitis B surface antigen [HBsAb]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (HBsAb positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR - Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
- •Any history of another cancer during the last 5 years with the exception of non-melanoma skin tumors, in situ cervical carcinoma, or in situ breast cancer treated with curative intent with no history of metastatic disease.
- •Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis or tuberculosis. Drugs for HIV treatment are allowed, as per local investigator prescription.
- •Active ongoing infection from SARS-CoV-2.
结局指标
主要结局
Overall Response Rate (ORR = Complete response, CR+ Partial response, PR) after induction cycle 1 (daratumumab alone), after induction cycles 3, 6 and 9 (end of induction, EOI); after maintenance cycles 12 and 15 (end of treatment, EOT). Response will be defined according to the Lugano 2014 criteria. The best response achieved per patient will be considered for analysis.
Overall Response Rate (ORR = Complete response, CR+ Partial response, PR) after induction cycle 1 (daratumumab alone), after induction cycles 3, 6 and 9 (end of induction, EOI); after maintenance cycles 12 and 15 (end of treatment, EOT). Response will be defined according to the Lugano 2014 criteria. The best response achieved per patient will be considered for analysis.
次要结局
- Progression-free survival (PFS), defined as the time from treatment start and progression/relapse or death from any cause (Lugano 2014)
- Overall survival (OS), defined as the time from treatment start and death from any cause (Lugano 2014).
- Duration of response (DOR), defined for all patients who achieved a response (CR or PR) according to Response Criteria for NHL CT-based and/or PET-based (Lugano 2014), and is measured from the date when criteria for response are met (CR or PR) until the date of progression or relapse.
- Role of daratumumab maintenance in terms of conversion rate of SD to PR or from SD/PR to CR.
- Association between intensity of CD38 expression and response. The extent of CD38 expression evaluated by immunochemistry will be correlated with response measured according to the Lugano 2014 criteria at various timepoints.
- Endpoints of the biological study: Impact of daratumumab/bortezomib treatment in immune activation, T cell differentiation, MDSC by multiparametric flow cytometry.
- Endpoints of the biological study: Impact of daratumumab/bortezomib treatment on the level of pro- and anti-inflammatory cytokines by Luminex technology.
- Endpoints of the biological study: Analysis of tumor microenvironment by ICH/alternative methods.
研究者
Andrés Ferreri, Prof.
Scientific
Fondazione Italiana Linfomi Ets
研究点 (21)
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