Patients with Relapsed or Refractory Plasmablastic lymphoma (PBL). MedDRA version: 21.1 Level: PT Classification code 10065039 Term: Plasmablastic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: DARZALEX
Product Name: Daratumumab
Product Code: [IMP 1]
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Curre
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. 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. b. 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; c. ECOG Performance Status less than or equal to 3; d. Age greater than or equal to 18 years; e. Both HIV-negative and HIV-positive patients are eligible; f. HIV infection responsive to ongoing cART (combination antiretroviral therapy); g. 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. h. 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 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. i. Subject understands and voluntarily signs and dates an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures j. Subject must be able to adhere to the study visit schedule and other protocol requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: a. Histologic diagnosis different from confirmed plasmablastic lymphoma according to WHO 2017 and/or CD38 expression 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 470 msec l. Evidence of any other clinically significant uncontrolled condition(s) m. Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: •To evaluate the efficacy in terms of Progression-free survival (PFS); •To evaluate the efficacy in terms of Overall survival (OS); •To evaluate the efficacy in terms of Duration of response (DOR); •To evaluate the safety of daratumumab as single agent and in combination with bortezomib/dexamethasone. •To assess the role of daratumumab maintenance; •To evaluate the association between intensity of CD38 expression and response.;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: From the date of beginning of treatment to the last response evaluation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: From treatment start to evidence of disease progression or death for any cause.; From treatment start to death.; From the date when criteria for response are met (CR or PR) until the date of progression or relapse.; From evidence of Stable Disease (SD) to evidence of Partial Response (PR) or from SD/PR to Complete Response (CR).; All treatment response assessment timepoints listed in the study.;Secondary end point(s): 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. | — |
Countries
Italy
Contacts
Public ContactUfficio start up
Fondazione Italiana Linfomi Onlus
Outcome results
None listed