Study of Entospletinib (ENTO) in Newly Diagnosed DLBCL Patients With aaIPI>=1 Treated by Chemiotherapy
- Conditions
- DLBCL
- Interventions
- Registration Number
- NCT03225924
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
-
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
- Alkaline phosphatase (in absence of bone disease), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 X ULN
-
Adequate renal function as calculated by a creatinine clearance > 40 ml/min by local institutional formula
-
Patients with prior Hepatitis B must be given antiviral prophylaxis and hepatitis B virus (HBV) DNA monitored; Patients with prior Hepatitis C are eligible if, hepatitis C virus (HCV) RNA is undetectable.
-
Left ventricular ejection fraction (LVEF) ≥ 50% of echocardiography or multiple gated acquisition (MUGA) scan
-
Adequate tissue for central retrospective testing for cell of origin (10-15 slides of tumor biopsy must be available at baseline)
-
Heterosexually active females of childbearing potential (as defined in the protocol) must:
- have a negative serum pregnancy test at baseline and prior to the first study drug administration (C1D-4)
- have practiced at least 1 reliable method of contraception for at least 2 months prior to the first study drug administration (C1D-4)
- agree to utilize highly effective methods of contraception (as defined in the protocol) from Cycle 1 Day -4 until 12 months following the last treatment administration
-
Heterosexually active males with partners of childbearing potential must agree to use reliable forms of contraception during treatment and up to 12 months after last treatment administration
-
Male subjects must agree to avoid sperm donation from Cycle 1 Day -4 until 12 months following the last treatment administration
-
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
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Active infection as judged by the investigator
-
Known hypersensitivity to ENTO
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Congenital immunodeficiency or known HIV (human immunodeficiency virus infection) or active viral hepatitis B or C
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Any other major illness that in the investigator's judgement, will substantially increase the risk associated with the subject's participation in the study
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Subjects who have undergone a solid organ transplant and stem cell transplant
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Previous treatment for B cell lymphoma or Richter's transformation
-
Primary Mediastinal B Cell Lymphoma
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental Vincristine Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone Experimental Doxorubicin Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone Experimental Rituximab Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone Experimental Cyclophosphamide Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone Experimental Prednisone Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone Experimental Entospletinib Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone
- Primary Outcome Measures
Name Time Method Phase II: Complete Metabolic Response (CMR) rate at the end of treatment 168 days To determine the CMR rate by the Lugano classification 2014 (Deauville scale 1-3) at the end of treatment
Phase I: recommended phase 2 dose 6 months To determine the recommended phase 2 dose for Entospletinib
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (27)
UCL Namur
🇧🇪Yvoir, Belgium
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
Az Groeninge
🇧🇪Kortrijk, Belgium
Clinique Universite Catholique de Louvain Saint-Luc
🇧🇪Bruxelles, Belgium
University Hospital Gent
🇧🇪Gent, Belgium
Hopital Joliment
🇧🇪Haine-Saint-Paul, Belgium
Ch de Bourg En Bresse
🇫🇷Bourg-en-Bresse, France
CHU Henri Mondor
🇫🇷Créteil, France
CHU Côte de Nacre
🇫🇷Caen, France
CHU Montpellier
🇫🇷Montpellier, France
Ch Region Mulhouse Et Sud Alsace
🇫🇷Mulhouse, France
Chu de Rennes - Pontchaillou
🇫🇷Rennes, France
Ch Annecy Genevois
🇫🇷Pringy, France
Chu de Reims - Hopital Robert Debre
🇫🇷Reims, France
Ch de Roubaix-Hopital Victor Provo
🇫🇷Roubaix, France
Ch de Valenciennes
🇫🇷Valenciennes, France
Chru de Nancy
🇫🇷Vandœuvre-lès-Nancy, France
CHU de Dijon
🇫🇷Dijon, France
Ch de Versailles - Hopital Andre Mignot
🇫🇷Le Chesnay, France
Clinique Victor Hugo
🇫🇷Le Mans, France
Chu de Limoges - Hopital Dupuytren
🇫🇷Limoges, France
Clinique de La Sauvegarde
🇫🇷Lyon, France
CHU Lyon Sud
🇫🇷Lyon, France
Chu de Bordeaux
🇫🇷Pessac, France
Hôpital Bretonneau- Centre H. Kaplan
🇫🇷Tours, France
Hopital Necker Paris
🇫🇷Paris, France
Iuct Oncopole de Toulouse
🇫🇷Toulouse, France