Last reviewed · How we verify

NCT00790036: PILLAR2

Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy

Completed Phase 3 Results posted Last updated 12 July 2017
What this trial tests

Phase 3 trial testing Everolimus in Diffuse Large B-cell Lymphoma in 742 participants. Completed in 15 June 2016.

Timeline
24 July 2009
Primary endpoint
15 June 2016
15 June 2016

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment742
Start date24 July 2009
Primary completion15 June 2016
Estimated completion15 June 2016
Sites202 locations across Hong Kong, Colombia, Italy, Japan, Poland, South Korea, Lebanon, New Zealand

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Diffuse Large B-cell 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.

Disease-free Survival (DFS) Primary · From date of randomization to the date of event defined as the first documented recurrence of the disease, or death due to any cause and up to 6 years

DFS was defined as the time from date of randomization to the date of event defined as the first documented relapse of the disease or death due to any cause. Relapse was based on investigator assessment and was assigned only if: It was documented according to Cheson guidelines by an objective radiological assessment method; It was documented by a biopsy proven lymphoma including new or recurrent bone marrow involvement; A new anticancer therapy for lymphoma started with subsequent confirmation of the relapse within 4 weeks of the start of this anticancer therapy

GroupValue95% CI
RAD001 (Everolimus)177.872.7 – 82.1
Placebo77.072.1 – 81.1
Overall Survival (OS) Secondary · From date of randomization to date of death due to any cause up to around 7 years

OS was defined as the time from date of randomization to date of death due to any cause. If the patient was not known to have died, survival was censored at the date of the last contact.

2 years
GroupValue95% CI
RAD001 (Everolimus)190.787.0 – 93.4
Placebo88.384.4 – 91.3
3 years
GroupValue95% CI
RAD001 (Everolimus)188.083.8 – 91.1
Placebo83.779.3 – 87.3
4 years
GroupValue95% CI
RAD001 (Everolimus)185.480.7 – 89.1
Placebo80.775.8 – 84.7
5 years
GroupValue95% CI
RAD001 (Everolimus)183.478.1 – 87.5
Placebo77.471.7 – 82.0
6 years
GroupValue95% CI
RAD001 (Everolimus)180.371.6 – 86.6
Placebo77.471.7 – 82.0
Lymphoma-specific Survival (LSS) Secondary · From randomization to death documented as a result of lymphoma up to 7 years

LSS was defined as time from randomization to death as a result of lymphoma.

2 years
GroupValue95% CI
RAD001 (Everolimus)194.991.8 – 96.8
Placebo90.586.9 – 93.2
3 years
GroupValue95% CI
RAD001 (Everolimus)193.189.6 – 95.5
Placebo88.884.9 – 91.8
4 years
GroupValue95% CI
RAD001 (Everolimus)191.687.6 – 94.3
Placebo86.982.6 – 90.3
5 years
GroupValue95% CI
RAD001 (Everolimus)189.484.6 – 92.8
Placebo85.480.5 – 89.2
6 years
GroupValue95% CI
RAD001 (Everolimus)189.484.6 – 92.8
Placebo85.480.5 – 89.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

RAD001 (Everolimus)
Serious: 105/368 (29%)
Deaths:
Placebo
Serious: 62/364 (17%)
Deaths:
All Patients
Serious: 167/732 (23%)
Deaths:

Serious adverse events (180 terms)

ReactionSystemRAD001 (Everolimus)PlaceboAll Patients
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Cardiac failureCardiac disorders
Cardiac failure congestiveCardiac disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Pneumocystis jirovecii pneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
AnaemiaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
StomatitisGastrointestinal disorders
Cholecystitis acuteHepatobiliary disorders
CellulitisInfections and infestations
GastroenteritisInfections and infestations
Hepatitis BInfections and infestations
Gamma-glutamyltransferase increasedInvestigations
DehydrationMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Other adverse events (45 terms — click to expand)

ReactionSystemRAD001 (Everolimus)PlaceboAll Patients
StomatitisGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Mouth ulcerationGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
HyperglycaemiaMetabolism and nutrition disorders
AstheniaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
CD4 lymphocytes decreasedInvestigations
HypercholesterolaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
LeukopeniaBlood and lymphatic system disorders
HypertriglyceridaemiaMetabolism and nutrition disorders
DizzinessNervous system disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
Urinary tract infectionInfections and infestations
Blood lactate dehydrogenase increasedInvestigations
EpistaxisRespiratory, thoracic and mediastinal disorders
LymphopeniaBlood and lymphatic system disorders
Weight decreasedInvestigations
SinusitisInfections and infestations
DysgeusiaNervous system disorders
HypertensionVascular disorders

Most-reported serious reactions: Febrile neutropenia, Neutropenia, Pneumonia, Cardiac failure, Cardiac failure congestive, Pyrexia, Dyspnoea, Pneumonitis.

Data from ClinicalTrials.gov NCT00790036 adverse events section.

Sponsor's own description

Phase III study of RAD001 adjuvant therapy in poor risk patients with Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 versus matching placebo after patients had achieved complete response with first-line rituximab-chemotherapy

Publications & conference data

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

  1. Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents.
    Cragg GM, Pezzuto JM. · · 2016 · cited 413× · PMID 26679767 · DOI 10.1159/000443404
  2. Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.
    Camicia R, Winkler HC, Hassa PO. · · 2015 · cited 137× · PMID 26654227 · DOI 10.1186/s12943-015-0474-2
  3. When less may be more: calorie restriction and response to cancer therapy.
    O'Flanagan CH, Smith LA, McDonell SB, Hursting SD. · · 2017 · cited 135× · PMID 28539118 · DOI 10.1186/s12916-017-0873-x
  4. Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era.
    Vaidya R, Witzig TE. · · 2014 · cited 130× · PMID 24625454 · DOI 10.1093/annonc/mdu109
  5. Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial.
    Johnston PB, LaPlant B, McPhail E, Habermann TM, et al · · 2016 · cited 48× · PMID 27374464 · DOI 10.1016/s2352-3026(16)30040-0
  6. Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial.
    Witzig TE, Tobinai K, Rigacci L, Ikeda T, et al · · 2018 · cited 47× · PMID 29253068 · DOI 10.1093/annonc/mdx764
  7. Targeting mTOR for the treatment of B cell malignancies.
    Lee JS, Vo TT, Fruman DA. · · 2016 · cited 30× · PMID 26805380 · DOI 10.1111/bcp.12888
  8. Altered pathways and targeted therapy in double hit lymphoma.
    Zhuang Y, Che J, Wu M, Guo Y, et al · · 2022 · cited 26× · PMID 35303910 · DOI 10.1186/s13045-022-01249-9

Verify or expand the search:

Other trials of Everolimus

Trials testing the same drug.

Other recruiting trials for Diffuse Large B-cell Lymphoma

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00790036.

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