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

NCT03931642 | Completed Phase 2 DMC

• 1 other identifier: FILOCLL13-BLINART
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 28

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.

Conditions

Richter Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

  From the first treatment administration and during treatment period (R-CHOP and blinatomomab)

• overall response

  At week 16 from baseline, after blinatumomab induction and at week 24 after blinatumomab consolidation.

• CR rate

  After blinatumomab consolidation (total of 4 weeks) at week 24 from the beginning of study treatment.

Study Arms (1)

R-CHOP- blinatumomab

EXPERIMENTAL

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.

Drug: RCHOP; Drug: Blinatumomab

Interventions

RCHOP DRUG

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.

R-CHOP- blinatumomab

Blinatumomab DRUG

Blinatumomab by continuous vein infusion

R-CHOP- blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Amgen: collaborator

Study Sites (28)

Chu Amiens

Amiens, 80054, France

Location

CHU ANGERS - Maladies du sang

Angers, 49933, France

Location

Ch Cote Basque

Bayonne, 64109, France

Location

Hopital Jean Minjoz

Besançon, 25000, France

Location

CH de Béziers - Hématologie

Béziers, 34500, France

Location

Hôpital Avicenne - Centre de Recherche Clinique

Bobigny, 93009, France

Location

CHU Caen - IHBN - Hématologie Clinique

Caen, 14033, France

Location

CHU Estaing - Hématologie Clinique Adulte

Clermont-Ferrand, 63000, France

Location

CHU Grenoble - Hématologie

Grenoble, 388043, France

Location

Centre Hospitalier du Mans

Le Mans, 72000, France

Location

Hôpital Saint Vicent de Paul

Lille, 59000, France

Location

Centre Léon Bérard - Hématologie

Lyon, 69373, France

Location

Institut Paoli-Calmettes - Hématologie Clinique

Marseille, 13273, France

Location

HOPITAL SAINT ELOI - Hematologie

Montpellier, 34295, France

Location

Hopital E.Muller

Mulhouse, 68100, France

Location

CHU DE NANTES - Hematologie clinique

Nantes, 44093, France

Location

Hopital Pitie Salpetriere Service Hematologie Clinique - Pavillon de L'Enfant Et Adolescent

Paris, 75651, France

Location

CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique

Perpignan, 66000, France

Location

Bordeaux Pessac

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire

Poitiers, 86021, France

Location

Hôpital Robert Debré - Hématologie Clinique

Reims, 51092, France

Location

CHU Pontchaillou - Hématologie Clinique BMT-HC

Rennes, 35033, France

Location

Centre Henri Becquerel - Service Hématologie Clinique

Rouen, 76038, France

Location

Hôpital Hautepierre - Hématologie

Strasbourg, 67098, France

Location

IUCT ONCOPOLE - Hématologie

Toulouse, 31059, France

Location

Hôpital Bretonneau - Hématologie et Thérapie Cellulaire

Tours, 37044, France

Location

Hôpitaux de Brabois - Hématologie Adulte

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Interventions

blinatumomab

Study Officials

• Romain GUIEZE

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 30, 2019
• Study Start: July 5, 2019
• Primary Completion: October 1, 2021
• Study Completion: October 21, 2022
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (28)