Brief Title
BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
Official Title
BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
Brief Summary
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Complete remission (CR) rate according to the revised Lugano criteria
Secondary Outcome
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
Condition
Richter Syndrome
Intervention
RCHOP
Study Arms / Comparison Groups
R-CHOP- blinatumomab
Description: Patients will first undergo a prior debulking therapy including 2 cycles of R-CHOP. At Day1 (D1) : Rituximab 375 mg/m² Intravenous (IV) + Cyclophosphamide 750 mg/m² IV + Doxorubicin 50 mg/m² IV + Vincristine 1.4 mg/m² IV. From D1 to D5 : Prednisone 60 mg/m² Per Os (PO). Patients with CR and no measurable lesion left will not be treated further in the setting of the present trial. All the remaining patients will be continuing and treating on study with a single cycle of blinatumomab induction therapy : Blinatumomab at 9 μg/d IV by continuous vein infusion from day 1-7, 28 μg/d from day 8-14 and 112 μg/d from day 15-56. Patients who achieve an objective response after induction are eligible to receive one further optional cycle of blinatumomab consolidation : blinatumomab 9 μg/d IV by continuous vein infusion from day 1-7, 28 μg/d from day 8-14 and 112 μg/day IV from day 15-28.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
41
Start Date
July 5, 2019
Completion Date
July 4, 2022
Primary Completion Date
October 1, 2021
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Romain GUIEZE, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT03931642
Organization ID
FILOCLL13-BLINART
Responsible Party
Sponsor
Study Sponsor
French Innovative Leukemia Organisation
Collaborators
Amgen
Study Sponsor
Romain GUIEZE, Principal Investigator, University Hospital, Clermont-Ferrand
Verification Date
February 2022