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DLBCLPhase 1/2NCT03225924

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

A Phase 1/2 study testing Entospletinib, Rituximab and Cyclophosphamide in people with DLBCL, run by The Lymphoma Academic Research Organisation at 27 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 60 to 80 years
Conditions the study is for
DLBCL
What is being tested?
Entospletinib, Rituximab and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
27 sitesin 2 countries
Study dates
26 Jul 2017to 18 Oct 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

27 sites in 2 countries.

27 sites in 2 countries

France21 sites

  • Ch de Bourg En Bresse

    Bourg-en-Bresse, 0100

  • CHU Côte de Nacre

    Caen

  • CHU Henri Mondor

    Créteil

  • CHU de Dijon

    Dijon

  • Ch de Versailles - Hopital Andre Mignot

    Le Chesnay, 78150

  • Clinique Victor Hugo

    Le Mans, 72000

  • Chu de Limoges - Hopital Dupuytren

    Limoges, 87042

  • Clinique de La Sauvegarde

    Lyon, 69337

  • CHU Lyon Sud

    Lyon

  • CHU Montpellier

    Montpellier

  • Ch Region Mulhouse Et Sud Alsace

    Mulhouse, 68070

  • Hopital Necker Paris

    Paris, 75015

  • Chu de Bordeaux

    Pessac, 33604

  • Ch Annecy Genevois

    Pringy, 74374

  • Chu de Reims - Hopital Robert Debre

    Reims, 51092

  • Chu de Rennes - Pontchaillou

    Rennes, 35033

  • Ch de Roubaix-Hopital Victor Provo

    Roubaix, 59056

  • Iuct Oncopole de Toulouse

    Toulouse, 31059

  • Hôpital Bretonneau- Centre H. Kaplan

    Tours, 37044

  • Ch de Valenciennes

    Valenciennes, 59322

  • Chru de Nancy

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Belgium6 sites

  • Institut Jules Bordet

    Brussels, 1000

  • Clinique Universite Catholique de Louvain Saint-Luc

    Brussels, 1200

  • University Hospital Gent

    Ghent, 9000

  • Hopital Joliment

    Haine-Saint-Paul, 7100

  • Az Groeninge

    Kortrijk, 8500

  • UCL Namur

    Yvoir

Other trials in Belgium

About this study

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)

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
Being tested
Entospletinib, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EntospletinibDrug

    Also called ENTO

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

  • RituximabDrug

    Also called Mabthera

    cycles of 21 days - 375mg/m²

  • CyclophosphamideDrug

    cycles of 21 days - 750 mg/m²

  • DoxorubicinDrug

    cycles of 21 days - 50mg/m²

  • VincristineDrug

    cycles of 21 days - 1.4mg/m²

  • PrednisoneDrug

    cycles of 21 days - 40mg/m²

Study groups in NCT03225924
Study groupRoleWhat they receive
ExperimentalExperimentalEntospletinib + Rituximab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisone
Receives: Drug: Entospletinib; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: recommended phase 2 dose

    To determine the recommended phase 2 dose for Entospletinib

    Measured: 6 months

  2. Phase II: Complete Metabolic Response (CMR) rate at the end of treatment

    To determine the CMR rate by the Lugano classification 2014 (Deauville scale 1-3) at the end of treatment

    Measured: 168 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2017
  2. Study start26 Jul 2017
  3. Primary completion18 Oct 2019
  4. Study completion18 Oct 2019

Why it stopped: Stop of drug development

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03225924
Sponsor's protocol ID
ENTO-R-CHOP
Status last verified
Sep 2020
First submitted
20 Jul 2017
Last updated
2 Sep 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Entospletinib, Rituximab and Cyclophosphamide in people with DLBCL, run by The Lymphoma Academic Research Organisation at 27 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Stop of drug development). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: recommended phase 2 dose (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03225924.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2020; AzTrials last refreshed its copy on 7 Nov 2026.

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