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

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ClinicalTrials.gov Identifier: NCT03225924
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
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.


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)
Estimated Enrollment : 131 participants
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
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids
Drug Information available for: Rituximab

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




Primary Outcome Measures :
  1. Phase I: recommended phase 2 dose [ Time Frame: 6 months ]
    To determine the recommended phase 2 dose for Entospletinib

  2. 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



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Ages Eligible for Study:   60 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
Contact: Laetitia Melgar +334 72 66 93 33 laetitia.melgar@lysarc.org

Locations
Belgium
UCL Namur Recruiting
Yvoir, Belgium
Contact: Julien Depaus         
France
CHU Côte de Nacre Recruiting
Caen, France
Contact: Christophe Fruchart         
CHU Henri Mondor Recruiting
Créteil, France
Contact: Corinne Haioun         
CHU de Dijon Recruiting
Dijon, France
Contact: Olivier Casasnovas         
CHU Lyon Sud Recruiting
Lyon, France
Contact: Gilles Salles         
CHU Montpellier Recruiting
Montpellier, France
Contact: Emmanuelle Tchernonog         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Investigators
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     History of Changes
Other Study ID Numbers: ENTO-R-CHOP
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
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

Additional relevant MeSH terms:
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
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
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators