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
PILLAR2
A Randomized, Double-blind, Placebo-controlled, Multi-center 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
2 other identifiers
interventional
742
33 countries
197
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2009
Longer than P75 for phase_3
197 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 11, 2008
CompletedFirst Posted
Study publicly available on registry
November 13, 2008
CompletedStudy Start
First participant enrolled
July 24, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 15, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 15, 2016
CompletedResults Posted
Study results publicly available
July 12, 2017
CompletedJuly 12, 2017
June 1, 2017
6.9 years
November 11, 2008
June 14, 2017
June 14, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Disease-free Survival (DFS)
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
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
Secondary Outcomes (2)
Overall Survival (OS)
From date of randomization to date of death due to any cause up to around 7 years
Lymphoma-specific Survival (LSS)
From randomization to death documented as a result of lymphoma up to 7 years
Study Arms (2)
Everolimus
EXPERIMENTALParticipants who received Everolimus 10 mg (two 5 mg tablets), daily for 12 months
Placebo
PLACEBO COMPARATORParticipants who received Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months
Interventions
Everolimus was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.
Everolimus placebo was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.
Eligibility Criteria
You may qualify if:
- Patients defined as poor risk with IPI of 3, 4, or 5 at time of original diagnosis.
- Patients age ≥ 18 years old.
- Patients must have achieved complete remission (CR) based on the revised IWRC (Cheson et al 2007) following first line R-chemotherapy treatment. Radiation therapy (RT) during or after R-chemotherapy is acceptable provided: 1) it ends 4 weeks prior to start of study drug and, 2) in case of consolidation RT targeted at initial bulky tumor mass, administered after R-chemotherapy, patient is already in CR before initiating RT. Complete remission from R-chemotherapy must be confirmed by clinical and radiologic evaluation along with bone marrow confirmation (if bone marrow was involved by lymphoma before the R-chemotherapy treatment). Local pathology report on the bone marrow biopsy is acceptable. If bone marrow was not involved by lymphoma before R-chemotherapy treatment, then bone marrow confirmation after R-chemotherapy is not required.
- Patients who received a minimum 5 cycles of R-chemotherapy treatment and maximum 8 cycles of R-chemotherapy treatment. Any variation of CHOP (R-CHOP-14, R-CHOP-21) is acceptable. Liposomal doxorubicin, epirubicin, or pirarubicin (also known as therarubicin) is acceptable. R-EPOCH is acceptable.
- Patients' last treatment with R-chemotherapy must be 6 to 14 weeks prior to start of study drug.
- Patients with ECOG performance status (PS) 0, 1, or 2.
- Patients willing to provide a portion of his/her tumor tissue from original diagnosis or lymph node to confirm diagnosis.
- The following laboratory values obtained ≤ 21 days prior to start of study drug:
- Absolute neutrophil count ≥ 1000/mm3 (or 1.0 GI/L, SI units)
- Platelet count ≥ 100,000/mm3 (or 100 GI/L, SI units)
- Hemoglobin ≥ 9 g/dL (can be achieved by transfusion)
- Total bilirubin ≤ 2 x ULN (if \>2 x ULN direct bilirubin is required and should be ≤1.5 x ULN)
- AST ≤ 3 x ULN
- Serum creatinine ≤ 2 x ULN
- Women of childbearing potential must have had a negative serum pregnancy test 14 days prior to the start of study drug plus a negative local urine pregnancy test on Day 1, Cycle 1 prior to treatment and must be willing to use adequate methods of contraception during the study and for 8 weeks after study drug administration.
- +2 more criteria
You may not qualify if:
- Patients with evidence of disease according to the revised IWRC (Cheson et al 2007) after completion of the first-line R-chemotherapy treatment, prior to study entry.
- Patients receiving ongoing radiation therapy or who received radiation therapy to the residual tumor masses \< 4 weeks from start of study drug.
- Patients who have previously received systemic mTOR inhibitor (sirolimus, temsirolimus, everolimus, etc).
- Patients with evidence of current central nervous system (CNS) involvement with lymphoma. Patients who have only had prophylactic intrathecal chemotherapy against CNS disease are eligible.
- Patients with transformed follicular lymphoma.
- Patients who received ibritumomab tiuxetan (Zevalin®), in order to avoid potential delayed kidney toxicities.
- Patients who had myelosuppressive chemotherapy or biologic therapy \< 3 weeks from start of study drug.
- Patients receiving chronic systemic immunosuppressive agents. Inhaled and topical steroids are acceptable. Patients may be receiving stable (not increased within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg of prednisone or ≤5 mg of dexamethasone per day, if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency or asthma.
- Patients with active, bleeding diathesis.
- Patients with a known history of HIV seropositivity.
- Patients with known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to any of the excipients.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study drug, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before study drug start
- severely impaired lung function as defined as spirometry and DLCO that is ≤ 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
- poorly controlled diabetes as defined by fasting serum glucose \>2.0 x ULN
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (202)
Ironwood Cancer and Research Centers SC
Chandler, Arizona, 85224, United States
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, 72703, United States
University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (3)
La Jolla, California, 92093-0658, United States
USC/Kenneth Norris Comprehensive Cancer Center Dept.ofNorrisMedicalCenter(4)
Los Angeles, California, 90033, United States
University of Colorado Health
Colorado Springs, Colorado, 80909, United States
Denver Health & Hospital Authority CACZ885M2301
Denver, Colorado, 80204-4507, United States
Rocky Mountain Cancer Centers RMCC
Greenwood Village, Colorado, United States
University Cancer Institute
Boynton Beach, Florida, 33426, United States
University Cancer & Blood Center, LLC
Athens, Georgia, 30607, United States
Columbus Regional
Columbus, Georgia, 31904, United States
Rush University Medical Center Div. of Hematology & Oncology
Chicago, Illinois, 60612, United States
Indiana University Hospital IU Cancer Center
Indianapolis, Indiana, 46202, United States
Tulane University Health Sciences Center Office of Clinical Research
New Orleans, Louisiana, 70112, United States
Lahey Clinic Dept of Lahey Clinic (3)
Burlington, Massachusetts, 01805, United States
Mayo Clinic - Rochester Dept. of MayoClinic-Rochester
Rochester, Minnesota, 55905, United States
Washington University School of Medicine Div. of Medical Oncology
St Louis, Missouri, 63110, United States
Dartmouth Hitchcock Medical Center Dartmouth
Lebanon, New Hampshire, 03756, United States
Levine Cancer Institute Oncology
Charlotte, North Carolina, 28203, United States
Wake Forest University Baptist Medical Center Dept. of WFUHS
Winston-Salem, North Carolina, 27157, United States
University of Pittsburgh Medical Center SC-3
Pittsburgh, Pennsylvania, 15213, United States
Medical University of South Carolina -Hollings Cancer Center MUSC/HCC (2)
Charleston, South Carolina, 29425, United States
Cancer Centers of the Carolinas Cancer Centers of Carolinas (3
Greenville, South Carolina, 29605, United States
University of Tennessee Cancer Institute SC-2
Memphis, Tennessee, 38104, United States
The West Clinic
Memphis, Tennessee, 38120, United States
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD
Fort Worth, Texas, 76104, United States
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (18)
Houston, Texas, 77030-4009, United States
Baylor College of Medicine Dept.of Baylor College of Med.
Houston, Texas, 77030, United States
South Texas Oncology and Hematology, PA South Texas Oncology (2)
San Antonio, Texas, 78258, United States
Texas A&M HealthSciencesCtr-Scott & White Memorial Hospital CenterForCancerPrevention&Care
Temple, Texas, 76508, United States
University of Vermont Office of Clinical Trials Res.
Burlington, Vermont, 05404, United States
University of Virginia Health Systems SC-2
Charlottesville, Virginia, 22908-0334, United States
Blue Ridge Research Center at Roanoke Neurological Center SC
Roanoke, Virginia, 24018, United States
Dean Health System
Madison, Wisconsin, 53717, United States
Waukesha Memorial Hospital Cancer Center Dept.ofWaukeshaMemorialHosp.
Waukesha, Wisconsin, 53188, United States
Novartis Investigative Site
La Plata, Buenos Aires, B1900AWT, Argentina
Novartis Investigative Site
Buenos Aires, C1114AAN, Argentina
Novartis Investigative Site
Córdoba, X5016KEH, Argentina
Novartis Investigative Site
Douglas, Queensland, 4810, Australia
Novartis Investigative Site
Greenslopes, Queensland, 4120, Australia
Novartis Investigative Site
Clayton, Victoria, 3168, Australia
Novartis Investigative Site
Geelong, Victoria, 3220, Australia
Novartis Investigative Site
Innsbruck, Tyrol, 6020, Austria
Novartis Investigative Site
Leoben, A-8700, Austria
Novartis Investigative Site
Linz, 4010, Austria
Novartis Investigative Site
Vienna, 1090, Austria
Novartis Investigative Site
Vienna, 1140, Austria
Novartis Investigative Site
Curitiba, Paraná, 80060-900, Brazil
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
Novartis Investigative Site
Campinas, São Paulo, 13083-970, Brazil
Novartis Investigative Site
São Paulo, São Paulo, 01224-000, Brazil
Novartis Investigative Site
São Paulo, São Paulo, 05403-000, Brazil
Novartis Investigative Site
Brampton, Ontario, L6R 3J7, Canada
Novartis Investigative Site
Cambridge, Ontario, N1R 3G2, Canada
Novartis Investigative Site
Mississauga, Ontario, L5M 2V8, Canada
Novartis Investigative Site
Ottawa, Ontario, K1H 8L6, Canada
Novartis Investigative Site
Toronto, Ontario, M4C 3E7, Canada
Novartis Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Novartis Investigative Site
Greenfield Park, Quebec, J4V 2H1, Canada
Novartis Investigative Site
Montreal, Quebec, H1T 2M4, Canada
Novartis Investigative Site
Montreal, Quebec, H4A 3J1, Canada
Novartis Investigative Site
Québec, Quebec, G1J 1Z4, Canada
Novartis Investigative Site
Chengdu, Sichuan, 610041, China
Novartis Investigative Site
Hangzhou, Zhejiang, 310003, China
Novartis Investigative Site
Beijing, 100021, China
Novartis Investigative Site
Beijing, 100036, China
Novartis Investigative Site
Guangzhou, 510060, China
Novartis Investigative Site
Shanghai, 200025, China
Novartis Investigative Site
Bogotá, Cundinamarca, Colombia
Novartis Investigative Site
Bucaramanga, Colombia
Novartis Investigative Site
Medellín, Colombia
Novartis Investigative Site
Brno-Bohunice, Czech Republic, 625 00, Czechia
Novartis Investigative Site
Hradec Králové, CZE, 500 05, Czechia
Novartis Investigative Site
Olomouc, CZE, 775 20, Czechia
Novartis Investigative Site
Prague, 100 34, Czechia
Novartis Investigative Site
Al Mansurah, 35516, Egypt
Novartis Investigative Site
Alexandria, Egypt
Novartis Investigative Site
Cairo, 11566, Egypt
Novartis Investigative Site
Cairo, 12655, Egypt
Novartis Investigative Site
Cairo, Egypt
Novartis Investigative Site
Amiens Cedex1, 80054, France
Novartis Investigative Site
Brest, 29200, France
Novartis Investigative Site
La Roche-sur-Yon, 85925, France
Novartis Investigative Site
Limoges, 87042, France
Novartis Investigative Site
Pessac, 33604, France
Novartis Investigative Site
Saint-Priest-en-Jarez, 42271, France
Novartis Investigative Site
Aachen, 52074, Germany
Novartis Investigative Site
Bad Saarow, 15526, Germany
Novartis Investigative Site
Bamberg, 96049, Germany
Novartis Investigative Site
Cologne, 51067, Germany
Novartis Investigative Site
Dresden, 01307, Germany
Novartis Investigative Site
Freiburg im Breisgau, 79106, Germany
Novartis Investigative Site
Hamburg, 20095, Germany
Novartis Investigative Site
München, 81737, Germany
Novartis Investigative Site
Heraklion Crete, Greece, 711 10, Greece
Novartis Investigative Site
Athens, GR, 115 27, Greece
Novartis Investigative Site
Ioannina, GR, 455 00, Greece
Novartis Investigative Site
Athens, 11527, Greece
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Budapest, 1122, Hungary
Novartis Investigative Site
Győr, H-9023, Hungary
Novartis Investigative Site
Kaposvár, 7400, Hungary
Novartis Investigative Site
Pécs, 7624, Hungary
Novartis Investigative Site
Szeged, H-6725, Hungary
Novartis Investigative Site
Haifa, 3525408, Israel
Novartis Investigative Site
Jerusalem, 91120, Israel
Novartis Investigative Site
Petah Tikva, 49100, Israel
Novartis Investigative Site
Ramat Gan, 5266202, Israel
Novartis Investigative Site
Tel Aviv, 64239, Israel
Novartis Investigative Site
Brindisi, BR, 72100, Italy
Novartis Investigative Site
Catania, CT, 95124, Italy
Novartis Investigative Site
San Giovanni Rotondo, FG, 71013, Italy
Novartis Investigative Site
Florence, FI, 50134, Italy
Novartis Investigative Site
Genova, GE, 16132, Italy
Novartis Investigative Site
Lecce, LE, 73100, Italy
Novartis Investigative Site
Milan, MI, 20141, Italy
Novartis Investigative Site
Rozzano, MI, 20089, Italy
Novartis Investigative Site
Modena, MO, 41100, Italy
Novartis Investigative Site
Palermo, PA, 90146, Italy
Novartis Investigative Site
Piacenza, PC, 29100, Italy
Novartis Investigative Site
Pescara, PE, 65124, Italy
Novartis Investigative Site
Pisa, PI, 56126, Italy
Novartis Investigative Site
Potenza, PZ, 85100, Italy
Novartis Investigative Site
Reggio Calabria, RC, 89124, Italy
Novartis Investigative Site
Reggio Emilia, RE, 42123, Italy
Novartis Investigative Site
Siena, SI, 53100, Italy
Novartis Investigative Site
Venezia, VE, 30174, Italy
Novartis Investigative Site
Nagoya, Aichi-ken, 466-8650, Japan
Novartis Investigative Site
Kashiwa, Chiba, 277-8577, Japan
Novartis Investigative Site
Matsuyama, Ehime, 790-8524, Japan
Novartis Investigative Site
Kure, Hiroshima, 737-0023, Japan
Novartis Investigative Site
Kanazawa, Ishikawa-ken, 920-8641, Japan
Novartis Investigative Site
Shinjuku-ku, Japan, 160-0023, Japan
Novartis Investigative Site
Kyoto, Kyoto, 602-8566, Japan
Novartis Investigative Site
Sendai, Miyagi, 980-8574, Japan
Novartis Investigative Site
Osaka, Osaka, 545-8586, Japan
Novartis Investigative Site
Suita, Osaka, 565-0871, Japan
Novartis Investigative Site
Sunto-gun, Shizuoka, 411-8777, Japan
Novartis Investigative Site
Chuo-ku, Tokyo, 104-0045, Japan
Novartis Investigative Site
Koto, Tokyo, 135-8550, Japan
Novartis Investigative Site
Fukuoka, 811-1395, Japan
Novartis Investigative Site
Beirut, 1107 2020, Lebanon
Novartis Investigative Site
Beirut, 166378, Lebanon
Novartis Investigative Site
Beirut, 166830, Lebanon
Novartis Investigative Site
Beirut, 6301, Lebanon
Novartis Investigative Site
Saida, 652, Lebanon
Novartis Investigative Site
Mexico City, Mexico City, 01120, Mexico
Novartis Investigative Site
Monterrey, Nuevo León, 64020, Mexico
Novartis Investigative Site
Grafton, Auckland, New Zealand
Novartis Investigative Site
Wellington, New Zealand
Novartis Investigative Site
Oslo, NO-0424, Norway
Novartis Investigative Site
Jesus Maria, Lima region, 11, Peru
Novartis Investigative Site
San Isidro, Lima region, 27, Peru
Novartis Investigative Site
Lublin, Lublin Voivodeship, 20-080, Poland
Novartis Investigative Site
Bydgoszcz, 85-796, Poland
Novartis Investigative Site
Lodz, 93-509, Poland
Novartis Investigative Site
Warsaw, 02-106, Poland
Novartis Investigative Site
Moscow, 115478, Russia
Novartis Investigative Site
Moscow, 125167, Russia
Novartis Investigative Site
Moscow, 129110, Russia
Novartis Investigative Site
Nizhny Novgorod, 603000, Russia
Novartis Investigative Site
Petrozavodsk, 185019, Russia
Novartis Investigative Site
Saint Petersburg, 191024, Russia
Novartis Investigative Site
Saint Petersburg, 197341, Russia
Novartis Investigative Site
Saint Petersburg, 197758, Russia
Novartis Investigative Site
Dammam, 15215, Saudi Arabia
Novartis Investigative Site
Jeddah, 21423, Saudi Arabia
Novartis Investigative Site
Riyadh, 11426, Saudi Arabia
Novartis Investigative Site
Singapore, 119228, Singapore
Novartis Investigative Site
Singapore, 169608, Singapore
Novartis Investigative Site
Singapore, 169610, Singapore
Novartis Investigative Site
Bratislava, 833 10, Slovakia
Novartis Investigative Site
Gyeonggi-do, Korea, 10408, South Korea
Novartis Investigative Site
Seoul, Korea, 03722, South Korea
Novartis Investigative Site
Seoul, Korea, 05505, South Korea
Novartis Investigative Site
Seoul, Korea, 06351, South Korea
Novartis Investigative Site
Cadiz, Andalusia, 11009, Spain
Novartis Investigative Site
Seville, Andalusia, 41013, Spain
Novartis Investigative Site
Sabadell, Barcelona, 08208, Spain
Novartis Investigative Site
Donostia / San Sebastian, Basque Country, 20080, Spain
Novartis Investigative Site
Santander, Cantabria, 39008, Spain
Novartis Investigative Site
Badalona, Catalonia, 08916, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08003, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08028, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
Majadahonda, Madrid, 28222, Spain
Novartis Investigative Site
Pozuelo de Alarcón, Madrid, 28223, Spain
Novartis Investigative Site
Pamplona, Navarre, 31008, Spain
Novartis Investigative Site
Valencia, Valencia, 46010, Spain
Novartis Investigative Site
Madrid, 28006, Spain
Novartis Investigative Site
Zurich, CH, 8091, Switzerland
Novartis Investigative Site
Bellinzona, 6500, Switzerland
Novartis Investigative Site
Bangkok, 10330, Thailand
Novartis Investigative Site
Bangkok, 10400, Thailand
Novartis Investigative Site
Bangkok, 10700, Thailand
Novartis Investigative Site
Songkhla, 90110, Thailand
Novartis Investigative Site
Ankara, 06100, Turkey (Türkiye)
Novartis Investigative Site
Ankara, 06460, Turkey (Türkiye)
Novartis Investigative Site
Antalya, 07070, Turkey (Türkiye)
Novartis Investigative Site
Istanbul, 34093, Turkey (Türkiye)
Novartis Investigative Site
Talas / Kayseri, 38039, Turkey (Türkiye)
Novartis Investigative Site
Caracas, Distrito Federal, 1010, Venezuela
Novartis Investigative Site
Caracas, Distrito Federal, 1011, Venezuela
Related Publications (1)
Witzig TE, Tobinai K, Rigacci L, Ikeda T, Vanazzi A, Hino M, Shi Y, Mayer J, Costa LJ, Bermudez Silva CD, Zhu J, Belada D, Bouabdallah K, Kattan JG, Kuruvilla J, Kim WS, Larouche JF, Ogura M, Ozcan M, Fayad L, Wu C, Fan J, Louveau AL, Voi M, Cavalli F. Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial. Ann Oncol. 2018 Mar 1;29(3):707-714. doi: 10.1093/annonc/mdx764.
PMID: 29253068DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 11, 2008
First Posted
November 13, 2008
Study Start
July 24, 2009
Primary Completion
June 15, 2016
Study Completion
June 15, 2016
Last Updated
July 12, 2017
Results First Posted
July 12, 2017
Record last verified: 2017-06