DARATUMUMAB for Plasmablastic lymphoma

Inclusion criteria

• {"criterion_text":"-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."}
• {"criterion_text":"-Subject must be able to adhere to the study visit schedule and other protocol requirements"}
• {"criterion_text":"-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;"}
• {"criterion_text":"-ECOG Performance Status ≤ 3;"}
• {"criterion_text":"-Age ≥ 18 years;"}
• {"criterion_text":"-Both HIV-negative and HIV-positive patients are eligible;"}
• {"criterion_text":"-HIV infection responsive to ongoing cART (combination antiretroviral therapy);"}
• {"criterion_text":"-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."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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"}

Exclusion criteria

• {"criterion_text":"-Histologic diagnosis different from confirmed plasmablastic lymphoma according to WHO 2017 and/or CD38 expression < 5% of positive cells"}
• {"criterion_text":"-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"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Evidence of any other clinically significant uncontrolled condition(s)"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Breastfeeding women or women with a positive pregnancy test at screening"}
• {"criterion_text":"-CNS involvement"}
• {"criterion_text":"-Patients with known hypersensitivity to the investigational drug or to product components or severe allergic or anaphylactic reactions to humanized products"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Concomitant Kaposi sarcoma; however, patients with only skin involvement of KS can be included."}
• {"criterion_text":"-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)"}
• {"criterion_text":"-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."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Active ongoing infection from SARS-CoV-2."}

Primary endpoints

• {"endpoint_text":"-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.","definition_or_measurement_approach":"Response will be defined according to the Lugano 2014 criteria. The best response achieved per patient will be considered for analysis; assessed after specified induction and maintenance cycles (cycle 1, cycles 3/6/9, cycles 12/15)."}

Secondary endpoints

• {"endpoint_text":"-Progression-free survival (PFS), defined as the time from treatment start and progression/relapse or death from any cause (Lugano 2014)","definition_or_measurement_approach":"Defined as time from treatment start to progression/relapse or death from any cause; assessed according to Lugano 2014 criteria."}
• {"endpoint_text":"-Overall survival (OS), defined as the time from treatment start and death from any cause (Lugano 2014).","definition_or_measurement_approach":"Defined as time from treatment start to death from any cause; assessed per Lugano 2014."}
• {"endpoint_text":"-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.","definition_or_measurement_approach":"Measured from date when CR or PR criteria are first met until date of progression or relapse; per Lugano 2014 CT-/PET-based criteria."}
• {"endpoint_text":"-Role of daratumumab maintenance in terms of conversion rate of SD to PR or from SD/PR to CR.","definition_or_measurement_approach":"Conversion rates during maintenance (e.g., SD→PR, SD/PR→CR) measured using Lugano 2014 response assessments at timepoints."}
• {"endpoint_text":"-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.","definition_or_measurement_approach":"Correlation analysis between percent/intensity of CD38 expression by immunohistochemistry and response per Lugano 2014 at specified timepoints."}
• {"endpoint_text":"-Endpoints of the biological study: Impact of daratumumab/bortezomib treatment in immune activation, T cell differentiation, MDSC by multiparametric flow cytometry.","definition_or_measurement_approach":"Immune activation, T cell differentiation, and MDSC assessed by multiparametric flow cytometry as defined in biological study procedures."}
• {"endpoint_text":"-Endpoints of the biological study: Impact of daratumumab/bortezomib treatment on the level of pro- and anti-inflammatory cytokines by Luminex technology.","definition_or_measurement_approach":"Cytokine levels measured using Luminex technology to assess pro- and anti-inflammatory cytokine profiles."}
• {"endpoint_text":"-Endpoints of the biological study: Analysis of tumor microenvironment by ICH/alternative methods.","definition_or_measurement_approach":"Tumor microenvironment analysis performed by immunohistochemistry and/or alternative methods as specified in the biological study."}

Italy

Earliest CTIS Part Ii Submission Date

16-11-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

485

Number Of Sites

19

Number Of Participants

28

Primary sponsor

Full Name

Fondazione Italiana Linfomi Ets

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Janssen-Cilag SpA","duties_or_roles":"Monetary support","organisation_type":""}