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NCT02568683

Safety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

Terminated Phase 1, PHASE2 Results posted Last updated 17 April 2019
What this trial tests

Phase 1, PHASE2 trial testing Entospletinib in Non-Hodgkin Lymphoma in 10 participants. Terminated before completion.

Timeline
11 February 2016
Primary endpoint
3 October 2016
22 June 2017

Quick facts

Lead sponsorGilead Sciences
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment10
Start date11 February 2016
Primary completion3 October 2016
Estimated completion22 June 2017
Sites7 locations across France, United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Non-Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AEs) and Laboratory (Lab) Abnormalities Defined as Dose Limiting Toxicities (DLTs) in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage Primary · Cycle 1 (28-day cycle)

Occurrence of any of the following toxicities during Cycle 1 was considered DLT if judged by the Investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen: * Grade 4 (or higher) non-hematologic toxicity * Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care * Note: Grade 3 or higher neuropathy was considered DLT if occurring during Cycle 1 regardless of duration. * Any Grade 3 non-hematologic laboratory value if: * Medical intervention was required to treat the patient, or * Abnormality led to h

GroupValue95% CI
ENTO 200 mg0
ENTO 400 mg2
Number of Participants With AEs and Lab Abnormalities Not Defined as DLTs in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage Secondary · Cycle 1 (28-day cycle)

The number of participants with AEs and lab abnormalities not defined as DLTs in participants in the dose escalation stage with relapsed or refractory B-cell NHL are presented.

AEs not defined as DLTs
GroupValue95% CI
ENTO 200 mg6
ENTO 400 mg4
Lab abnormalities not defined as DLTs
GroupValue95% CI
ENTO 200 mg5
ENTO 400 mg4
Duration of Exposure to ENTO Secondary · Baseline to end of study (maximum: 24 weeks)
GroupValue95% CI
ENTO 200 mg17.7± 6.09
ENTO 400 mg4.3± 2.68
Number of VCR Doses Secondary · Baseline to end of study (maximum: 24 weeks)
GroupValue95% CI
ENTO 200 mg8.7± 3.27
ENTO 400 mg2.3± 1.50

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to the last dose date plus 30 days (maximum exposure: 200 mg ENTO = 24 weeks; 400 mg ENTO = 8 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

ENTO 200 mg
Serious: 1/6 (17%)
Deaths:
ENTO 400 mg
Serious: 1/4 (25%)
Deaths:

Serious adverse events (2 terms)

ReactionSystemENTO 200 mgENTO 400 mg
PyrexiaGeneral disorders
Sinus painRespiratory, thoracic and mediastinal disorders
Other adverse events (48 terms — click to expand)

ReactionSystemENTO 200 mgENTO 400 mg
DiarrhoeaGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Seasonal allergyImmune system disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
DysphagiaGastrointestinal disorders
IleusGastrointestinal disorders
OdynophagiaGastrointestinal disorders
AstheniaGeneral disorders
Feeling drunkGeneral disorders
Ill-defined disorderGeneral disorders
MalaiseGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood creatinine increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Weight decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Groin painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Disturbance in attentionNervous system disorders
HeadacheNervous system disorders
HypoaesthesiaNervous system disorders
Neuropathy peripheralNervous system disorders
ParaesthesiaNervous system disorders
AgitationPsychiatric disorders
Confusional statePsychiatric disorders
Mental status changesPsychiatric disorders
DysuriaRenal and urinary disorders

Most-reported serious reactions: Pyrexia, Sinus pain.

Data from ClinicalTrials.gov NCT02568683 adverse events section.

Sponsor's own description

The primary objective of this study is to evaluate the safety of ENTO with VCR in participants with relapsed or refractory B-cell NHL.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Syk inhibitors in clinical development for hematological malignancies.
    Liu D, Mamorska-Dyga A. · · 2017 · cited 130× · PMID 28754125 · DOI 10.1186/s13045-017-0512-1
  2. Targeting B-cell receptor signaling kinases in chronic lymphocytic leukemia: the promise of entospletinib.
    Sharman J, Di Paolo J. · · 2016 · cited 28× · PMID 27247756 · DOI 10.1177/2040620716636542
  3. SYK Targeting Represents a Potential Therapeutic Option for Relapsed Resistant Pediatric <i>ETV6-RUNX1</i> B-Acute Lymphoblastic Leukemia Patients.
    Serafin V, Porcù E, Cortese G, Mariotto E, et al · · 2019 · cited 9× · PMID 31817853 · DOI 10.3390/ijms20246175
  4. Novel agents in follicular lymphoma: choosing the best target.
    Sehn LH. · · 2016 · PMID 27913493 · DOI 10.1182/asheducation-2016.1.284

Verify or expand the search:

Other trials of Entospletinib

Trials testing the same drug.

Other recruiting trials for Non-Hodgkin Lymphoma

Currently open trials in the same condition.

Other Gilead Sciences trials

Trials by the same sponsor.

Verify against primary sources

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing