Study of Entospletinib (ENTO) in Newly Diagnosed DLBCL Patients With aaIPI>=1 Treated by Chemiotherapy

NCT03225924 | Terminated Phase 1 DMC

• 1 other identifier: ENTO-R-CHOP
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 27

Brief Summary

The primary objective of the phase Ib of the study is to determine the recommended phase 2 dose (RP2D) for entospletinib (ENTO) in patients treated with R-CHOP. The primary objective of the phase II is to determine the complete metabolic response (CMR) rate by the Lugano classification 2014 (Deauville scale 1-3) at the end of treatment.

Conditions

DLBCL

Outcome Measures

Primary Outcomes (2)

• Phase I: recommended phase 2 dose

  To determine the recommended phase 2 dose for Entospletinib

  6 months

• Phase II: Complete Metabolic Response (CMR) rate at the end of treatment

  To determine the CMR rate by the Lugano classification 2014 (Deauville scale 1-3) at the end of treatment

  168 days

Study Arms (1)

Experimental

EXPERIMENTAL

Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone

Drug: Entospletinib; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Interventions

Entospletinib DRUG

200mg or 400mg twice a day for 7 days every 21 cycles - total of 8 cycles

Also known as: ENTO

Experimental

Rituximab DRUG

cycles of 21 days - 375mg/m²

Also known as: Mabthera

Experimental

Cyclophosphamide DRUG

cycles of 21 days - 750 mg/m²

Experimental

Doxorubicin DRUG

cycles of 21 days - 50mg/m²

Experimental

Vincristine DRUG

cycles of 21 days - 1.4mg/m²

Experimental

Prednisone DRUG

cycles of 21 days - 40mg/m²

Experimental

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed de novo DLBCL (CD20 positive) (cf section 20.6 - Appendix 4)
• Age between 60 and 80 years included, on the day of the informed consent document signature
• Age adjusted International Prognosis Index (aaIPI) score ≥ 1
• No prior treatment for DLBCL. However prephase treatment with 1mg/kg/day prednisone or equivalent, for a maximum of 14 days, is permitted prior to begin the treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (0 or 1 only for phase 1b)
• Life expectancy of ≥ 90 days (3 months) before starting Entospletinib
• Signed informed consent
• At least one bi-dimensionally measurable lesion defined as at least one node or tumor lesion on CT scan ≥ 1.5 cm
• fluorodeoxyglucose (FDG) positron emission tomography (PET-CT) performed at baseline with a FDG positive result
• Adequate hematologic functions defined as follows (unless secondary to bone marrow involvement by lymphoma):
• Absolute neutrophil count (ANC) \> 1.5 X 10\^9 G/l and
• Platelets count ≥ 75 X 10\^9/l without platelet transfusion dependency during the last 7 days and
• Haemoglobin level \> 9 g/dl (may receive transfusion)
• Adequate liver function defined as follows:
• Total bilirubin \<1.5 upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome and

You may not qualify if:

• Central nervous system or meningeal involvement with DLBCL
• Contraindication to any drug contained in the chemotherapy regimen
• Prior treatment with Entospletinib or other spleen tyrosine kinase (SYK ) inhibitor
• Patients with a prior history of other malignancy, exceptions include:
• a subject who has been disease-free after curative local treatment (surgical resection) for at least 3 years,
• a subject with a history of a completely resected non-melanoma skin cancer or in situ carcinoma with surgical complete excision.
• Patients taking current therapy with proton pump inhibitors and current therapy with medicines that are strong Cytochrome P450 3A (CYP3A) or CYP2C9 inducers, or moderate CYP2C9 inducers.
• Ongoing active pneumonitis
• Peripheral sensory or motor neuropathy grade \> 1.
• Major surgery within 4 weeks before first dose of study drug (minor procedures including transcutaneous biopsy, central line placement are permitted at any time)
• Inability to take oral medication or malabsorption syndrome or any other uncontrolled gastrointestinal condition that would impair ability to take entospletinib
• Significant cardiovascular impairment: congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of first dose of entospletinib or ventricular arrhythmia
• Active infection as judged by the investigator
• Known hypersensitivity to ENTO
• Congenital immunodeficiency or known HIV (human immunodeficiency virus infection) or active viral hepatitis B or C

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead

Study Sites (27)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Clinique Universite Catholique de Louvain Saint-Luc

Brussels, 1200, Belgium

Location

University Hospital Gent

Ghent, 9000, Belgium

Location

Hopital Joliment

Haine-Saint-Paul, 7100, Belgium

Location

Az Groeninge

Kortrijk, 8500, Belgium

Location

UCL Namur

Yvoir, Belgium

Location

Ch de Bourg En Bresse

Bourg-en-Bresse, 0100, France

Location

CHU Côte de Nacre

Caen, France

Location

CHU Henri Mondor

Créteil, France

Location

CHU de Dijon

Dijon, France

Location

Ch de Versailles - Hopital Andre Mignot

Le Chesnay, 78150, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Chu de Limoges - Hopital Dupuytren

Limoges, 87042, France

Location

Clinique de La Sauvegarde

Lyon, 69337, France

Location

CHU Lyon Sud

Lyon, France

Location

CHU Montpellier

Montpellier, France

Location

Ch Region Mulhouse Et Sud Alsace

Mulhouse, 68070, France

Location

Hopital Necker Paris

Paris, 75015, France

Location

Chu de Bordeaux

Pessac, 33604, France

Location

Ch Annecy Genevois

Pringy, 74374, France

Location

Chu de Reims - Hopital Robert Debre

Reims, 51092, France

Location

Chu de Rennes - Pontchaillou

Rennes, 35033, France

Location

Ch de Roubaix-Hopital Victor Provo

Roubaix, 59056, France

Location

Iuct Oncopole de Toulouse

Toulouse, 31059, France

Location

Hôpital Bretonneau- Centre H. Kaplan

Tours, 37044, France

Location

Ch de Valenciennes

Valenciennes, 59322, France

Location

Chru de Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Interventions

6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Gilles Salles

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

• Emmanuelle Tchernonog

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

• Julien Depaus

  UCL Namur

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: July 21, 2017
• Study Start: July 26, 2017
• Primary Completion: October 18, 2019
• Study Completion: October 18, 2019
• Last Updated: September 2, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (6); FR (21)