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NCT03135028: Japanese AML

Entospletinib (ENTO) as Monotherapy and in Combination With Chemotherapy in Japanese Adults

Terminated Phase 1 Results posted Last updated 6 March 2020
What this trial tests

Phase 1 trial testing Entospletinib in Hematologic Malignancy in 9 participants. Terminated before completion.

Timeline
19 May 2017
Primary endpoint
26 February 2019
26 February 2019

Quick facts

Lead sponsorGilead Sciences
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment9
Start date19 May 2017
Primary completion26 February 2019
Estimated completion26 February 2019
Sites6 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Hematologic Malignancy or Acute Myeloid Leukemia. 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.

Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) Primary · Cycle 1 (28-day cycle)

Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT: * Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue. * In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC \> 500/μL) or platelet count (\>25000/μL) within 28 days * Grade 4, clinically significant, electrolyte abnormalities that were

GroupValue95% CI
ENTO 400 mg0.0
Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT Secondary · Day 1 Up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks)
GroupValue95% CI
ENTO 400 mg100.0
Plasma Concentration of ENTO Secondary · Cycle 1 (28-days cycle) Day 8 at 0 (predose), 1, 2, 3, 4, 6, 8, and 12 hours postdose

Plasma concentration of drug (ENTO) over different time points is reported.

Cycle 1 Day 8, predose
GroupValue95% CI
ENTO 400 mg921.9± 610.47
Cycle 1 Day 8, 1 hour postdose
GroupValue95% CI
ENTO 400 mg1395.7± 1081.40
Cycle 1 Day 8, 2 hours postdose
GroupValue95% CI
ENTO 400 mg1892.7± 1285.08
Cycle 1 Day 8, 3 hours postdose
GroupValue95% CI
ENTO 400 mg1529.1± 994.69
Cycle 1 Day 8, 4 hours postdose
GroupValue95% CI
ENTO 400 mg1350.0± 862.21
Cycle 1 Day 8, 6 hours postdose
GroupValue95% CI
ENTO 400 mg1139.3± 709.22
Cycle 1 Day 8, 8 hours postdose
GroupValue95% CI
ENTO 400 mg1075.9± 659.08
Cycle 1 Day 8, 12 hours postdose
GroupValue95% CI
ENTO 400 mg855.1± 568.18

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

ENTO 400 mg
Serious: 4/9 (44%)
Deaths: 6/9

Serious adverse events (10 terms)

ReactionSystemENTO 400 mg
AnaemiaBlood and lymphatic system disorders
CataractEye disorders
Choroidal haemorrhageEye disorders
PyrexiaGeneral disorders
Hepatic function abnormalHepatobiliary disorders
Clostridium difficile colitisInfections and infestations
Enterococcal infectionInfections and infestations
PneumoniaInfections and infestations
HyphaemaInjury, poisoning and procedural complications
Diabetes mellitusMetabolism and nutrition disorders
Other adverse events (54 terms — click to expand)

ReactionSystemENTO 400 mg
NauseaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
DeliriumPsychiatric disorders
StomatitisGastrointestinal disorders
PyrexiaGeneral disorders
Blood bilirubin increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Disseminated intravascular coagulationBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
TachycardiaCardiac disorders
CataractEye disorders
Conjunctival haemorrhageEye disorders
GlaucomaEye disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
Gingival bleedingGastrointestinal disorders
MelaenaGastrointestinal disorders
OedemaGeneral disorders
Oedema peripheralGeneral disorders
NasopharyngitisInfections and infestations
Oral herpesInfections and infestations
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
Allergic transfusion reactionInjury, poisoning and procedural complications
Skin abrasionInjury, poisoning and procedural complications
Amylase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Lipase increasedInvestigations
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HyperammonaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Anaemia, Cataract, Choroidal haemorrhage, Pyrexia, Hepatic function abnormal, Clostridium difficile colitis, Enterococcal infection, Pneumonia.

Data from ClinicalTrials.gov NCT03135028 adverse events section.

Sponsor's own description

The primary objective of this study is to evaluate the safety and tolerability of entospletinib (ENTO) monotherapy and in combination with chemotherapy in Japanese participants.

Publications & conference data

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

  1. Combinatorial efficacy of entospletinib and chemotherapy in patient-derived xenograft models of infant acute lymphoblastic leukemia.
    Loftus JP, Yahiaoui A, Brown PA, Niswander LM, et al · · 2021 · cited 22× · PMID 32414848 · DOI 10.3324/haematol.2019.241729
  2. Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics.
    Roussel X, Daguindau E, Berceanu A, Desbrosses Y, et al · · 2020 · cited 14× · PMID 33363031 · DOI 10.3389/fonc.2020.599933

Verify or expand the search:

Other trials of Entospletinib

Trials testing the same drug.

Other recruiting trials for Hematologic Malignancy

Currently open trials in the same condition.

Other Gilead Sciences trials

Trials by the same sponsor.

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