Clinical trial NCT03931642: BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
Official title: BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Richter Syndrome
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2019-04-30
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Complete remission (CR) rate according to the revised Lugano criteria
timeFrame: at week 16 from baseline
Secondary outcomes:
measure: Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: From the first treatment administration and during treatment period (R-CHOP and blinatomomab)
measure: overall response
timeFrame: At week 16 from baseline, after blinatumomab induction and at week 24 after blinatumomab consolidation.
measure: CR rate
timeFrame: After blinatumomab consolidation (total of 4 weeks) at week 24 from the beginning of study treatment.
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens
city: Angers
country: France
facility: CHU ANGERS - Maladies du sang
city: Bayonne
country: France
facility: Ch Cote Basque
city: Besançon
country: France
facility: Hopital Jean Minjoz
city: Bobigny
country: France
facility: Hôpital Avicenne - Centre de Recherche Clinique
city: Béziers
country: France
facility: CH de Béziers - Hématologie
city: Caen
country: France
facility: CHU Caen - IHBN - Hématologie Clinique
city: Clermont-Ferrand
country: France
facility: CHU Estaing - Hématologie Clinique Adulte
city: Grenoble
country: France
facility: CHU Grenoble - Hématologie
city: Le Mans
country: France
facility: Centre Hospitalier du Mans
city: Lille
country: France
facility: Hôpital Saint Vicent de Paul
city: Lyon
country: France
facility: Centre Léon Bérard - Hématologie
city: Marseille
country: France
facility: Institut Paoli-Calmettes - Hématologie Clinique
city: Montpellier
country: France
facility: HOPITAL SAINT ELOI - Hematologie
city: Mulhouse
country: France
facility: Hopital E.Muller
city: Nantes
country: France
facility: CHU DE NANTES - Hematologie clinique
city: Paris
country: France
facility: Hopital Pitie Salpetriere Service Hematologie Clinique - Pavillon de L'Enfant Et Adolescent
city: Perpignan
country: France
facility: CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique
city: Pessac
country: France
facility: Bordeaux Pessac
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire
city: Reims
country: France
facility: Hôpital Robert Debré - Hématologie Clinique
city: Rennes
country: France
facility: CHU Pontchaillou - Hématologie Clinique BMT-HC
city: Rouen
country: France
facility: Centre Henri Becquerel - Service Hématologie Clinique
city: Strasbourg
country: France
facility: Hôpital Hautepierre - Hématologie
city: Toulouse
country: France
facility: IUCT ONCOPOLE - Hématologie
city: Tours
country: France
facility: Hôpital Bretonneau - Hématologie et Thérapie Cellulaire
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpitaux de Brabois - Hématologie Adulte
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Romain GUIEZE
role: PRINCIPAL_INVESTIGATOR
References: