Study of Entospletinib (ENTO) in Newly Diagnosed DLBCL Patients With aaIPI>=1 Treated by Chemiotherapy
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03225924 |
Recruitment Status :
Terminated
(Stop of drug development)
First Posted : July 21, 2017
Last Update Posted : September 2, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
DLBCL | Drug: Entospletinib Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 25 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official 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) |
Actual Study Start Date : | July 26, 2017 |
Actual Primary Completion Date : | October 18, 2019 |
Actual Study Completion Date : | October 18, 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: Experimental
Entospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone
|
Drug: Entospletinib
200mg or 400mg twice a day for 7 days every 21 cycles - total of 8 cycles
Other Name: ENTO Drug: Rituximab cycles of 21 days - 375mg/m²
Other Name: Mabthera Drug: Cyclophosphamide cycles of 21 days - 750 mg/m² Drug: Doxorubicin cycles of 21 days - 50mg/m² Drug: Vincristine cycles of 21 days - 1.4mg/m² Drug: Prednisone cycles of 21 days - 40mg/m² |
- Phase I: recommended phase 2 dose [ Time Frame: 6 months ]To determine the recommended phase 2 dose for Entospletinib
- Phase II: Complete Metabolic Response (CMR) rate at the end of treatment [ Time Frame: 168 days ]To determine the CMR rate by the Lugano classification 2014 (Deauville scale 1-3) at the end of treatment

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 60 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Any other major illness that in the investigator's judgement, will substantially increase the risk associated with the subject's participation in the study
- Subjects who have undergone a solid organ transplant and stem cell transplant
- Previous treatment for B cell lymphoma or Richter's transformation
- Primary Mediastinal B Cell Lymphoma

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03225924

Principal Investigator: | Gilles Salles | Hospices Civils de Lyon | |
Principal Investigator: | Emmanuelle Tchernonog | University Hospital, Montpellier | |
Principal Investigator: | Julien Depaus | UCL Namur |
Responsible Party: | The Lymphoma Academic Research Organisation |
ClinicalTrials.gov Identifier: | NCT03225924 |
Other Study ID Numbers: |
ENTO-R-CHOP |
First Posted: | July 21, 2017 Key Record Dates |
Last Update Posted: | September 2, 2020 |
Last Verified: | September 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Lymphoma, Large B-Cell, Diffuse Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Prednisone Cyclophosphamide Rituximab Doxorubicin Vincristine |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Anti-Inflammatory Agents |