BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
Blinatumomab (BLINCYTO) is a bi-specific T-cell engaging (BiTE®) antibody construct that
 transiently links CD3-positive T cells to CD19-positive B-cells, inducing T-cell activation
 and subsequent lysis of tumor cells.

 The investigators propose to evaluate the efficacy, safety and tolerability of blinatumomab
 administered after R-CHOP debulking therapy in patients with Richter Syndrome (RS) of diffuse
 large B-cell lymphoma (DLBCL) histology.

 The investigators hypothesize that 8-week blinatumomab induction therapy leads to Complete
 Response (CR) rate improvement (revised Cheson criteria) from a baseline of 7percent as
 observed in the prospective study evaluating R-CHOP.
Inclusion Criteria:

 -  Confirmed diagnosis of chronic lymphocytic leukemia (CLL) 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

 -  Eastern Cooperative Oncology Group (ECOG) performance 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
 (HSCT) 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

 Exclusion Criteria:

 -  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 cerebrospinal fluid analysis)

 -  Steroids treatment (≥ 20 mg for one week) before inclusion

 -  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) serum glutamate
 oxaloacetate transaminase and/or serum glutamate pyruvate transaminase and/or alkaline
 phosphatase > 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