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

NCT ID: NCT03225924

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-26
• Study Completion Date: 2019-10-18

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone

Group Type: EXPERIMENTAL

Entospletinib

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

cycles of 21 days - 375mg/m²

Cyclophosphamide

Intervention Type: DRUG

cycles of 21 days - 750 mg/m²

Doxorubicin

Intervention Type: DRUG

cycles of 21 days - 50mg/m²

Vincristine

Intervention Type: DRUG

cycles of 21 days - 1.4mg/m²

Prednisone

Intervention Type: DRUG

cycles of 21 days - 40mg/m²

Interventions

Entospletinib

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

Intervention Type: DRUG

Rituximab

cycles of 21 days - 375mg/m²

Intervention Type: DRUG

Cyclophosphamide

cycles of 21 days - 750 mg/m²

Intervention Type: DRUG

Doxorubicin

cycles of 21 days - 50mg/m²

Intervention Type: DRUG

Vincristine

cycles of 21 days - 1.4mg/m²

Intervention Type: DRUG

Prednisone

cycles of 21 days - 40mg/m²

Intervention Type: DRUG

Other Intervention Names

ENTO; Mabthera

Eligibility Criteria

Inclusion Criteria

1. Patients with histologically confirmed de novo DLBCL (CD20 positive) (cf section 20.6 - Appendix 4)

2. Age between 60 and 80 years included, on the day of the informed consent document signature

3. Age adjusted International Prognosis Index (aaIPI) score ≥ 1

4. 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

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (0 or 1 only for phase 1b)

6. Life expectancy of ≥ 90 days (3 months) before starting Entospletinib

7. Signed informed consent

8. At least one bi-dimensionally measurable lesion defined as at least one node or tumor lesion on CT scan ≥ 1.5 cm

9. fluorodeoxyglucose (FDG) positron emission tomography (PET-CT) performed at baseline with a FDG positive result

10. 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)

11. 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

12. Adequate renal function as calculated by a creatinine clearance > 40 ml/min by local institutional formula

13. 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.

14. Left ventricular ejection fraction (LVEF) ≥ 50% of echocardiography or multiple gated acquisition (MUGA) scan

15. Adequate tissue for central retrospective testing for cell of origin (10-15 slides of tumor biopsy must be available at baseline)

16. 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

17. 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

18. Male subjects must agree to avoid sperm donation from Cycle 1 Day -4 until 12 months following the last treatment administration

Exclusion Criteria

1. Central nervous system or meningeal involvement with DLBCL

2. Contraindication to any drug contained in the chemotherapy regimen

3. Prior treatment with Entospletinib or other spleen tyrosine kinase (SYK ) inhibitor

4. 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.

5. 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.

6. Ongoing active pneumonitis

7. Peripheral sensory or motor neuropathy grade > 1.

8. Major surgery within 4 weeks before first dose of study drug (minor procedures including transcutaneous biopsy, central line placement are permitted at any time)

9. Inability to take oral medication or malabsorption syndrome or any other uncontrolled gastrointestinal condition that would impair ability to take entospletinib

10. 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

11. Active infection as judged by the investigator

12. Known hypersensitivity to ENTO

13. Congenital immunodeficiency or known HIV (human immunodeficiency virus infection) or active viral hepatitis B or C

14. Any other major illness that in the investigator's judgement, will substantially increase the risk associated with the subject's participation in the study

15. Subjects who have undergone a solid organ transplant and stem cell transplant

16. Previous treatment for B cell lymphoma or Richter's transformation

17. Primary Mediastinal B Cell Lymphoma

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles Salles

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Emmanuelle Tchernonog

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Julien Depaus

Role: PRINCIPAL_INVESTIGATOR

UCL Namur

Locations

Institut Jules Bordet

Brussels, , Belgium

Clinique Universite Catholique de Louvain Saint-Luc

Brussels, , Belgium

University Hospital Gent

Ghent, , Belgium

Hopital Joliment

Haine-Saint-Paul, , Belgium

Az Groeninge

Kortrijk, , Belgium

UCL Namur

Yvoir, , Belgium

Ch de Bourg En Bresse

Bourg-en-Bresse, , France

CHU Côte de Nacre

Caen, , France

CHU Henri Mondor

Créteil, , 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 Montpellier

Montpellier, , France

Ch Region Mulhouse Et Sud Alsace

Mulhouse, , France

Hopital Necker Paris

Paris, , France

Chu de Bordeaux

Pessac, , France

Ch Annecy Genevois

Pringy, , France

Chu de Reims - Hopital Robert Debre

Reims, , France

Chu de Rennes - Pontchaillou

Rennes, , France

Ch de Roubaix-Hopital Victor Provo

Roubaix, , France

Iuct Oncopole de Toulouse

Toulouse, , France

Hôpital Bretonneau- Centre H. Kaplan

Tours, , France

Ch de Valenciennes

Valenciennes, , France

Chru de Nancy

Vandœuvre-lès-Nancy, , France

Countries

Belgium; France

Other Identifiers

ENTO-R-CHOP

Identifier Type: -

Identifier Source: org_study_id