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NCT01732913: Yosemite

Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Terminated Phase 3 Results posted Last updated 16 November 2018
What this trial tests

Phase 3 trial testing Placebo in Indolent Non-Hodgkin's Lymphomas in 295 participants. Terminated before completion.

Timeline
16 January 2013
Primary endpoint
18 May 2016
18 May 2016

Quick facts

Lead sponsorGilead Sciences
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment295
Start date16 January 2013
Primary completion18 May 2016
Estimated completion18 May 2016
Sites103 locations across Italy, Japan, Taiwan, Poland, South Korea, Russia, Sweden, Portugal

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

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

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 27 months plus 30 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Idelalisib + Rituximab
Serious: 103/198 (52%)
Deaths:
Placebo + Rituximab
Serious: 11/95 (12%)
Deaths:

Serious adverse events (110 terms)

ReactionSystemIdelalisib + RituximabPlacebo + Rituximab
PneumoniaInfections and infestations
DiarrhoeaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
PyrexiaGeneral disorders
ColitisGastrointestinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
SepsisInfections and infestations
Acute kidney injuryRenal and urinary disorders
Urinary tract infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Drug-induced liver injuryHepatobiliary disorders
SyncopeNervous system disorders
Transient ischaemic attackNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Cardiac failure congestiveCardiac disorders
AstheniaGeneral disorders
Hepatic function abnormalHepatobiliary disorders
JaundiceHepatobiliary disorders
Cytomegalovirus infectionInfections and infestations
Other adverse events (40 terms — click to expand)

ReactionSystemIdelalisib + RituximabPlacebo + Rituximab
DiarrhoeaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
FatigueGeneral disorders
RashSkin and subcutaneous tissue disorders
Infusion related reactionInjury, poisoning and procedural complications
HeadacheNervous system disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
PruritusSkin and subcutaneous tissue disorders
Upper respiratory tract infectionInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
Abdominal painGastrointestinal disorders
Weight decreasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
AnaemiaBlood and lymphatic system disorders
Transaminases increasedInvestigations
DizzinessNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
ChillsGeneral disorders
Gamma-glutamyltransferase increasedInvestigations
DehydrationMetabolism and nutrition disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
NasopharyngitisInfections and infestations
AnxietyPsychiatric disorders
BronchitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pneumonia, Diarrhoea, Alanine aminotransferase increased, Aspartate aminotransferase increased, Pyrexia, Colitis, Pneumonitis, Febrile neutropenia.

Data from ClinicalTrials.gov NCT01732913 adverse events section.

Sponsor's own description

The primary objective of this study is to evaluate the effect of the addition of idelalisib to rituximab on progression-free survival (PFS) in adults with previously treated indolent non-Hodgkin lymphoma (iNHL). An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line iNHL treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).

Publications & conference data

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

  1. Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer.
    Lim HJ, Crowe P, Yang JL. · · 2015 · cited 131× · PMID 25146530 · DOI 10.1007/s00432-014-1803-3
  2. Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma.
    Djavaheri-Mergny M, Giuriato S, Tschan MP, Humbert M. · · 2019 · cited 34× · PMID 30704144 · DOI 10.3390/cells8020103
  3. Phosphoinositide 3-kinase inhibitors in lymphoma.
    Curran E, Smith SM. · · 2014 · cited 32× · PMID 25024054 · DOI 10.1097/cco.0000000000000113
  4. Splenic marginal zone lymphoma: a literature review of diagnostic and therapeutic challenges.
    Santos TSD, Tavares RS, Farias DLC. · · 2017 · cited 30× · PMID 28577652 · DOI 10.1016/j.bjhh.2016.09.014
  5. Idelalisib for the treatment of non-Hodgkin lymphoma.
    Graf SA, Gopal AK. · · 2016 · cited 24× · PMID 26818003 · DOI 10.1517/14656566.2016.1135130
  6. Idelalisib for the treatment of indolent non-Hodgkin lymphoma: a review of its clinical potential.
    Barrientos JC. · · 2016 · cited 19× · PMID 27274288 · DOI 10.2147/ott.s102573
  7. Combinations of idelalisib with rituximab and/or bendamustine in patients with recurrent indolent non-Hodgkin lymphoma.
    de Vos S, Wagner-Johnston ND, Coutre SE, Flinn IW, et al · · 2016 · cited 18× · PMID 29296805 · DOI 10.1182/bloodadvances.2016000976
  8. The PI3K∂-Selective Inhibitor Idelalisib Induces T- and NK-Cell Dysfunction Independently of B-Cell Malignancy-Associated Immunosuppression.
    Rohrbacher L, Brauchle B, Ogrinc Wagner A, von Bergwelt-Baildon M, et al · · 2021 · cited 15× · PMID 33790890 · DOI 10.3389/fimmu.2021.608625

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