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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03225924
• Date of registration: 20/07/2017
• Prospective Registration: Yes
• Primary sponsor: The Lymphoma Academic Research Organisation
• Public title: Study of Entospletinib (ENTO) in Newly Diagnosed DLBCL Patients With aaIPI>=1 Treated by Chemiotherapy
• Scientific title: Phase Ib - II Study of Entospletinib (ENTO) in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients With aaIPI>=1 Treated by Rituximab, Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (R-CHOP)
• Date of first enrolment: July 26, 2017
• Target sample size: 25
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03225924
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Belgium, France

Contacts

• Name: Emmanuelle Tchernonog
• Affiliation: University Hospital, Montpellier

• Name: Julien Depaus
• Affiliation: UCL Namur

• Name: Gilles Salles
• Affiliation: Hospices Civils de Lyon

Key inclusion & exclusion 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



Age minimum: 60 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

DLBCL

Intervention(s)

Drug: Doxorubicin

Drug: Cyclophosphamide

Drug: Prednisone

Drug: Entospletinib

Drug: Rituximab

Drug: Vincristine

Primary Outcome(s)

Phase II: Complete Metabolic Response (CMR) rate at the end of treatment [Time Frame: 168 days]

Phase I: recommended phase 2 dose [Time Frame: 6 months]

Secondary ID(s)

ENTO-R-CHOP

Source(s) of Monetary Support

Please refer to primary and secondary sponsors