BLINAtumomab after R-CHOP debulking therapy for patients with Richter Transformation.
- Conditions
- Richter transformationTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2018-003483-32-FR
- Lead Sponsor
- FILO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 35
Confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma according to the revised iwCLL criteria19 with biopsy proven transformation to diffuse large B-cell lymphoma, consistent with RS according to the 2016 WHO classification.
•Both patients with previously treated or treatment-naïve CLL are eligible
•Age greater than or equal to 18 years
•ECOG performans status <3
•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 =1.0 G/L, platelet count =50 G/L independent of transfusion within 7 days of screening
•Subject must have adequate coagulation, renal, and hepatic function at screening
•Adequate left ventricular ejection function (> 50 %)
•Patients who have undergone prior allogeneic hematopoietic stem-cell transplantation are eligible as long as they do not have significant active graft versus host disease and that their transplant day 0 is > 6 months from their first dose of protocol therapy
•Female patients of child bearing potential must have negative pregnancy test and use an effective method of birth control during treatment period and 48h thereafter; Males must use an effective method of birth control during treatment period and 48h thereafter.
•Ability to understand and the willingness to sign a written informed consent document
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 15
•Patients with the Hodgkin variant of RS
•Patients with previously treated RS
•History or presence of clinically relevant disorder affecting the central nervous system (CNS)
•Known active DLBCL in the CNS (confirmed by CSF analysis)
•Steroids treatment (= 20 mg for one week) before inclusion
•Allogeneic HSCT within 6 months before inclusion
•Active graft-versus-host disease
•History of other malignancies, except: i) malignancy treated with curative intent and with no recurrence over the last 5 years ii) adequately treated non-melanoma skin cancer without evidence of disease iii) adequately treated carcinoma in situ without evidence of 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)
•Abnormal screening laboratory values as defined as following: a) ALT (SGOT) and/or ALT (SGPT) and/or ALP > or =5 x upper limit of normal (ULN); b) Total bilirubin > or = 1.5 x ULN, unless due to Gilbert's disease; c) Creatinine > or = 2.0 x ULN or creatinine clearance <50 mL/min (calculated).
•Fertile male and female patients who cannot or do not wish to use an effective method of contraception during treatment and for 48h after the final treatment used for the purposes of the study
•Treatment with other investigational agent or participating to another trial within 30 days prior to entering the study
•No affiliated to social security
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: The secondary objectives are to investigate the safety and toxicity of blinatunomab after 2 cycles of R-CHOP, the overall response and the patient outcome. Our study also includes an exploratory objective aiming at deciphering the clonal relationship between CLL and RS and uncovering genetic drivers of transformation.;Main Objective: The primary objective of this sudy is to determine the objective response to one 8-week cycle of blinatumomab following a debulking therapy with R-CHOP in patients with RS.;Primary end point(s): Complete remission rate according to the revised Lugano criteria at week 16.;Timepoint(s) of evaluation of this end point: week 16
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): binatumomab toxicity (CTCAE v.4)<br> Overall response rate (ORR) (revised Lugano criteria) after the first and second cycle of blinatumomab,<br> CR rate (revised Lugano criteria) after the second cycle of blinatumomab,<br> progression free survival (PFS),<br> overall survival (OS),<br> time to next treatment (TTNT),<br> response duration<br> ;<br> Timepoint(s) of evaluation of this end point: - week 24<br> - end of follow up period<br>