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

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

Study Overview

• Status: Completed
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Everolimus; Drug: Everolimus Placebo

• Study Type: Interventional
• Enrollment (Actual): 742
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1114AAN
    • Novartis Investigative Site
  • Cordoba, Argentina, X5016KEH
    • Novartis Investigative Site
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, B1900AWT
      • Novartis Investigative Site
• Australia
  • Queensland
    • Douglas, Queensland, Australia, 4810
      • Novartis Investigative Site
    • Greenslopes, Queensland, Australia, 4120
      • Novartis Investigative Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
    • Geelong, Victoria, Australia, 3220
      • Novartis Investigative Site
• Austria
  • Leoben, Austria, A-8700
    • Novartis Investigative Site
  • Linz, Austria, 4010
    • Novartis Investigative Site
  • Wien, Austria, 1090
    • Novartis Investigative Site
  • Wien, Austria, 1140
    • Novartis Investigative Site
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Novartis Investigative Site
• Brazil
  • PR
    • Curitiba, PR, Brazil, 80060-900
      • Novartis Investigative Site
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Novartis Investigative Site
  • SP
    • Campinas, SP, Brazil, 13083-970
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 05403-000
      • Novartis Investigative Site
    • São Paulo, SP, Brazil, 01224-000
      • Novartis Investigative Site
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Novartis Investigative Site
    • Cambridge, Ontario, Canada, N1R 3G2
      • Novartis Investigative Site
    • Mississauga, Ontario, Canada, L5M 2V8
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4C 3E7
      • Novartis Investigative Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H4A 3J1
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Novartis Investigative Site
    • Québec, Quebec, Canada, G1J 1Z4
      • Novartis Investigative Site
• China
  • Beijing, China, 100021
    • Novartis Investigative Site
  • Beijing, China, 100036
    • Novartis Investigative Site
  • Guangzhou, China, 510060
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
• Colombia
  • Bucaramanga, Colombia
    • Novartis Investigative Site
  • Medellín, Colombia
    • Novartis Investigative Site
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia
      • Novartis Investigative Site
• Czechia
  • Praha 10, Czechia, 100 34
    • Novartis Investigative Site
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
    • Olomouc, CZE, Czechia, 775 20
      • Novartis Investigative Site
  • Czech Republic
    • Brno - Bohunice, Czech Republic, Czechia, 625 00
      • Novartis Investigative Site
• Egypt
  • Alexandria, Egypt
    • Novartis Investigative Site
  • Cairo, Egypt
    • Novartis Investigative Site
  • Cairo, Egypt, 11566
    • Novartis Investigative Site
  • Cairo, Egypt, 12655
    • Novartis Investigative Site
  • Mansoura, Egypt, 35516
    • Novartis Investigative Site
• France
  • Amiens cedex1, France, 80054
    • Novartis Investigative Site
  • Brest, France, 29200
    • Novartis Investigative Site
  • La Roche sur Yon cedex 9, France, 85925
    • Novartis Investigative Site
  • Limoges cedex, France, 87042
    • Novartis Investigative Site
  • Pessac, France, 33604
    • Novartis Investigative Site
  • Saint Priest en Jarez Cedex, France, 42271
    • Novartis Investigative Site
• Germany
  • Aachen, Germany, 52074
    • Novartis Investigative Site
  • Bad Saarow, Germany, 15526
    • Novartis Investigative Site
  • Bamberg, Germany, 96049
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Hamburg, Germany, 20095
    • Novartis Investigative Site
  • Koeln, Germany, 51067
    • Novartis Investigative Site
  • Muenchen, Germany, 81737
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 11527
    • Novartis Investigative Site
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Novartis Investigative Site
    • Ioannina, GR, Greece, 455 00
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1122
    • Novartis Investigative Site
  • Gyor, Hungary, H-9023
    • Novartis Investigative Site
  • Kaposvar, Hungary, 7400
    • Novartis Investigative Site
  • Pecs, Hungary, 7624
    • Novartis Investigative Site
  • Szeged, Hungary, H-6725
    • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3525408
    • Novartis Investigative Site
  • Jerusalem, Israel, 91120
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5266202
    • Novartis Investigative Site
  • Tel Aviv, Israel, 64239
    • Novartis Investigative Site
• Italy
  • BR
    • Brindisi, BR, Italy, 72100
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95124
      • Novartis Investigative Site
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • LE
    • Lecce, LE, Italy, 73100
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41100
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90146
      • Novartis Investigative Site
  • PC
    • Piacenza, PC, Italy, 29100
      • Novartis Investigative Site
  • PE
    • Pescara, PE, Italy, 65124
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Novartis Investigative Site
  • PZ
    • Potenza, PZ, Italy, 85100
      • Novartis Investigative Site
  • RC
    • Reggio Calabria, RC, Italy, 89124
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Novartis Investigative Site
  • VE
    • Venezia, VE, Italy, 30174
      • Novartis Investigative Site
• Japan
  • Fukuoka, Japan, 811-1395
    • Novartis Investigative Site
  • Shinjuku-ku, Japan, 160-0023
    • Novartis Investigative Site
  • Aichi
    • Nagoya-city, Aichi, Japan, 466-8650
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Novartis Investigative Site
  • Ehime
    • Matsuyama-city, Ehime, Japan, 790-8524
      • Novartis Investigative Site
  • Hiroshima
    • Kure, Hiroshima, Japan, 737-0023
      • Novartis Investigative Site
  • Ishikawa
    • Kanazawa-city, Ishikawa, Japan, 920-8641
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 602-8566
      • Novartis Investigative Site
  • Miyagi
    • Sendai-city, Miyagi, Japan, 980-8574
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 545-8586
      • Novartis Investigative Site
    • Suita-city, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Novartis Investigative Site
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Novartis Investigative Site
    • Koto, Tokyo, Japan, 135-8550
      • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Gyeonggi-do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 06351
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03722
      • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 1107 2020
    • Novartis Investigative Site
  • Beirut, Lebanon, 6301
    • Novartis Investigative Site
  • Beirut, Lebanon, 166378
    • Novartis Investigative Site
  • Beirut, Lebanon, 166830
    • Novartis Investigative Site
  • Saida, Lebanon, 652
    • Novartis Investigative Site
• Mexico
  • Distrito Federal
    • México, Distrito Federal, Mexico, 01120
      • Novartis Investigative Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64020
      • Novartis Investigative Site
• New Zealand
  • Wellington, New Zealand
    • Novartis Investigative Site
  • Auckland
    • Grafton, Auckland, New Zealand
      • Novartis Investigative Site
• Norway
  • Oslo, Norway, NO-0424
    • Novartis Investigative Site
• Peru
  • Lima
    • Jesus Maria, Lima, Peru, 11
      • Novartis Investigative Site
    • San Isidro, Lima, Peru, 27
      • Novartis Investigative Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Novartis Investigative Site
  • Lodz, Poland, 93-509
    • Novartis Investigative Site
  • Warsaw, Poland, 02-106
    • Novartis Investigative Site
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-080
      • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Moscow, Russian Federation, 125167
    • Novartis Investigative Site
  • Moscow, Russian Federation, 129110
    • Novartis Investigative Site
  • N. Novgorod, Russian Federation, 603000
    • Novartis Investigative Site
  • Petrozavodsk, Russian Federation, 185019
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197341
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 191024
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
• Saudi Arabia
  • Dammam, Saudi Arabia, 15215
    • Novartis Investigative Site
  • Jeddah, Saudi Arabia, 21423
    • Novartis Investigative Site
  • Riyadh, Saudi Arabia, 11426
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Novartis Investigative Site
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 833 10
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Andalucía
    • Cadiz, Andalucía, Spain, 11009
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08028
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Novartis Investigative Site
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
  • Pais Vasco
    • San Sebastian, Pais Vasco, Spain, 20080
      • Novartis Investigative Site
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Novartis Investigative Site
  • CH
    • Zürich, CH, Switzerland, 8091
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Songkla, Thailand, 90110
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Ankara, Turkey, 06460
    • Novartis Investigative Site
  • Antalya, Turkey, 07070
    • Novartis Investigative Site
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
  • Talas / Kayseri, Turkey, 38039
    • Novartis Investigative Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers SC
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group Dept of Highlands Oncology Grp
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (3)
    • Los Angeles, California, United States, 90033
      • USC/Kenneth Norris Comprehensive Cancer Center Dept.ofNorrisMedicalCenter(4)
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • University of Colorado Health
    • Denver, Colorado, United States, 80204-4507
      • Denver Health & Hospital Authority CACZ885M2301
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • University Cancer Institute
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Columbus, Georgia, United States, 31904
      • Columbus Regional
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center Div. of Hematology & Oncology
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital IU Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center Office of Clinical Research
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Dept of Lahey Clinic (3)
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester Dept. of MayoClinic-Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Div. of Medical Oncology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center Dartmouth
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Cancer Institute Oncology
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center Dept. of WFUHS
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center SC-3
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina -Hollings Cancer Center MUSC/HCC (2)
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas Cancer Centers of Carolinas (3
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The West Clinic
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute SC-2
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD
    • Houston, Texas, United States, 77030-4009
      • University of Texas/MD Anderson Cancer Center Dept of MD Anderson (18)
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Dept.of Baylor College of Med.
    • San Antonio, Texas, United States, 78258
      • South Texas Oncology and Hematology, PA South Texas Oncology (2)
    • Temple, Texas, United States, 76508
      • Texas A&M HealthSciencesCtr-Scott & White Memorial Hospital CenterForCancerPrevention&Care
  • Vermont
    • Burlington, Vermont, United States, 05404
      • University of Vermont Office of Clinical Trials Res.
  • Virginia
    • Charlottesville, Virginia, United States, 22908-0334
      • University of Virginia Health Systems SC-2
    • Roanoke, Virginia, United States, 24018
      • Blue Ridge Research Center at Roanoke Neurological Center SC
  • Wisconsin
    • Madison, Wisconsin, United States, 53717
      • Dean Health System
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital Cancer Center Dept.ofWaukeshaMemorialHosp.
• Venezuela
  • Distrito Capital
    • Caracas, Distrito Capital, Venezuela, 1010
      • Novartis Investigative Site
    • Caracas, Distrito Capital, Venezuela, 1011
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with previous histologically confirmed Stage III-IV (or Stage II bulky disease, defined as any tumor mass more than 10 cm in longest diameter), at time of original diagnosis, diffuse large B cell lymphoma (pathology report based on original tumor tissue/lymph node is acceptable for meeting inclusion criteria, but tumor tissue (slides/block) must be available to be sent for central pathology to confirm diagnosis).
2. Patients defined as poor risk with IPI of 3, 4, or 5 at time of original diagnosis.
3. Patients age ≥ 18 years old.
4. 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.
5. 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.
6. Patients' last treatment with R-chemotherapy must be 6 to 14 weeks prior to start of study drug.
7. Patients with ECOG performance status (PS) 0, 1, or 2.
8. Patients willing to provide a portion of his/her tumor tissue from original diagnosis or lymph node to confirm diagnosis.

9. 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
10. 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.
11. Patients who give a written informed consent obtained according to local guidelines.
12. Patients capable of swallowing intact study medication tablets and following directions regarding taking study drug, or have a daily caregiver who will be responsible for administering study drug.

Exclusion Criteria:

1. 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.
2. Patients receiving ongoing radiation therapy or who received radiation therapy to the residual tumor masses < 4 weeks from start of study drug.
3. Patients who have previously received systemic mTOR inhibitor (sirolimus, temsirolimus, everolimus, etc).
4. 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.
5. Patients with transformed follicular lymphoma.
6. Patients who received ibritumomab tiuxetan (Zevalin®), in order to avoid potential delayed kidney toxicities.
7. Patients who had myelosuppressive chemotherapy or biologic therapy < 3 weeks from start of study drug.
8. 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.
9. Patients with active, bleeding diathesis.
10. Patients with a known history of HIV seropositivity.
11. Patients with known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to any of the excipients.

12. 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
    • any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
    • nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study drug, such as severe hypertension that is not controlled with medical management and thyroid abnormalities whose thyroid function cannot be maintained in the normal range by medication
    • liver disease such as cirrhosis or decompensated liver disease.
13. Patients who have a history of another primary malignancy ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine cervix.
14. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes.
15. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study drug start.
16. Patients unwilling to or unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus; Participants who received Everolimus 10 mg (two 5 mg tablets), daily for 12 months	Drug: Everolimus; Everolimus was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.; Other Names: RAD001
Placebo Comparator: Placebo; Participants who received Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months	Drug: Everolimus Placebo; Everolimus placebo was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	From date of randomization to date of death due to any cause up to around 7 years
Lymphoma-specific Survival (LSS)	LSS was defined as time from randomization to death as a result of lymphoma.	From randomization to death documented as a result of lymphoma up to 7 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2009
• Primary Completion (Actual): June 15, 2016
• Study Completion (Actual): June 15, 2016

Study Registration Dates

• First Submitted: November 11, 2008
• First Submitted That Met QC Criteria: November 12, 2008
• First Posted (Estimate): November 13, 2008

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: June 14, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: lymphoma; adjuvant therapy; Diffuse large B cell lymphoma; DLBCL; B-cell lymphoma; Hodgkin's; blood cancer; lymph nodes; poor risk; R-IPI 3-5; after R-CHOP or R-EPOCH; after R-CHOP; b cells; non-Hodgkin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CRAD001N2301; 2008-000498-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No