BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation

Richter Syndrome Clinical Trial

Official title:

BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03931642
• Other study ID #: FILOCLL13-BLINART
• Status: Completed
• Phase: Phase 2
• Start date: July 5, 2019
• Est. completion date: October 21, 2022

Study information

• Verified date: May 2023
• Source: French Innovative Leukemia Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: October 21, 2022
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Richter Syndrome

Intervention

Drug:
• RCHOP
D1 : Rituximab 375 mg/m² 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 PO.
• Blinatumomab
Blinatumomab by continuous vein infusion

Locations

Country	Name	City	State
France	Chu Amiens	Amiens
France	CHU ANGERS - Maladies du sang	Angers
France	Ch Cote Basque	Bayonne
France	Hopital Jean Minjoz	Besançon
France	CH de Béziers - Hématologie	Béziers
France	Hôpital Avicenne - Centre de Recherche Clinique	Bobigny
France	CHU Caen - IHBN - Hématologie Clinique	Caen
France	CHU Estaing - Hématologie Clinique Adulte	Clermont-Ferrand
France	CHU Grenoble - Hématologie	Grenoble
France	Centre Hospitalier du Mans	Le Mans
France	Hôpital Saint Vicent de Paul	Lille
France	Centre Léon Bérard - Hématologie	Lyon
France	Institut Paoli-Calmettes - Hématologie Clinique	Marseille
France	HOPITAL SAINT ELOI - Hematologie	Montpellier
France	Hopital E.Muller	Mulhouse
France	CHU DE NANTES - Hematologie clinique	Nantes
France	Hopital Pitie Salpetriere Service Hematologie Clinique - Pavillon de L'Enfant Et Adolescent	Paris
France	CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique	Perpignan
France	Bordeaux Pessac	Pessac
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire	Poitiers
France	Hôpital Robert Debré - Hématologie Clinique	Reims
France	CHU Pontchaillou - Hématologie Clinique BMT-HC	Rennes
France	Centre Henri Becquerel - Service Hématologie Clinique	Rouen
France	Hôpital Hautepierre - Hématologie	Strasbourg
France	IUCT ONCOPOLE - Hématologie	Toulouse
France	Hôpital Bretonneau - Hématologie et Thérapie Cellulaire	Tours
France	Hôpitaux de Brabois - Hématologie Adulte	Vandœuvre-lès-Nancy

Sponsors (2)

Lead Sponsor	Collaborator
French Innovative Leukemia Organisation	Amgen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission (CR) rate according to the revised Lugano criteria	the objective response rate to one 8-week cycle of blinatumomab following a debulking therapy with 2 R-CHOP cycles	at week 16 from baseline
Secondary	Number of patients with treatment-related adverse events as assessed by CTCAE v4.0	safety and toxicity of blinatumomab after 2 cycles of R-CHOP	From the first treatment administration and during treatment period (R-CHOP and blinatomomab)
Secondary	overall response	Overall response rate (revised Lugano criteria) after the first and second cycle of blinatumomab,	At week 16 from baseline, after blinatumomab induction and at week 24 after blinatumomab consolidation.
Secondary	CR rate	CR rate (revised Lugano criteria) after the second cycle of blinatumomab	After blinatumomab consolidation (total of 4 weeks) at week 24 from the beginning of study treatment.