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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00790036




Registration number
NCT00790036
Ethics application status
Date submitted
11/11/2008
Date registered
13/11/2008

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
2008-000498-40
Secondary ID [2] 0 0
CRAD001N2301
Universal Trial Number (UTN)
Trial acronym
PILLAR2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Everolimus
Treatment: Drugs - Everolimus Placebo

Experimental: Everolimus - Participants who received Everolimus 10 mg (two 5 mg tablets), daily for 12 months

Placebo comparator: Placebo - Participants who received Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months


Treatment: Drugs: Everolimus
Everolimus was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.

Treatment: Drugs: Everolimus Placebo
Everolimus placebo was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease-free Survival (DFS)
Timepoint [1] 0 0
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 [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From date of randomization to date of death due to any cause up to around 7 years
Secondary outcome [2] 0 0
Lymphoma-specific Survival (LSS)
Timepoint [2] 0 0
From randomization to death documented as a result of lymphoma up to 7 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/07/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/06/2016
Sample size
Target
Accrual to date
Final
742
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Douglas
Recruitment hospital [2] 0 0
Novartis Investigative Site - Greenslopes
Recruitment hospital [3] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [4] 0 0
Novartis Investigative Site - Geelong
Recruitment postcode(s) [1] 0 0
4810 - Douglas
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Hampshire
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Vermont
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Argentina
State/province [22] 0 0
Buenos Aires
Country [23] 0 0
Argentina
State/province [23] 0 0
Cordoba
Country [24] 0 0
Austria
State/province [24] 0 0
Tyrol
Country [25] 0 0
Austria
State/province [25] 0 0
Leoben
Country [26] 0 0
Austria
State/province [26] 0 0
Linz
Country [27] 0 0
Austria
State/province [27] 0 0
Wien
Country [28] 0 0
Brazil
State/province [28] 0 0
PR
Country [29] 0 0
Brazil
State/province [29] 0 0
RS
Country [30] 0 0
Brazil
State/province [30] 0 0
SP
Country [31] 0 0
Canada
State/province [31] 0 0
Ontario
Country [32] 0 0
Canada
State/province [32] 0 0
Quebec
Country [33] 0 0
China
State/province [33] 0 0
Sichuan
Country [34] 0 0
China
State/province [34] 0 0
Zhejiang
Country [35] 0 0
China
State/province [35] 0 0
Beijing
Country [36] 0 0
China
State/province [36] 0 0
Guangzhou
Country [37] 0 0
China
State/province [37] 0 0
Shanghai
Country [38] 0 0
Colombia
State/province [38] 0 0
Cundinamarca
Country [39] 0 0
Colombia
State/province [39] 0 0
Bucaramanga
Country [40] 0 0
Colombia
State/province [40] 0 0
Medellín
Country [41] 0 0
Czechia
State/province [41] 0 0
Czech Republic
Country [42] 0 0
Czechia
State/province [42] 0 0
CZE
Country [43] 0 0
Czechia
State/province [43] 0 0
Praha 10
Country [44] 0 0
Egypt
State/province [44] 0 0
Alexandria
Country [45] 0 0
Egypt
State/province [45] 0 0
Cairo
Country [46] 0 0
Egypt
State/province [46] 0 0
Mansoura
Country [47] 0 0
France
State/province [47] 0 0
Amiens cedex1
Country [48] 0 0
France
State/province [48] 0 0
Brest
Country [49] 0 0
France
State/province [49] 0 0
La Roche sur Yon cedex 9
Country [50] 0 0
France
State/province [50] 0 0
Limoges cedex
Country [51] 0 0
France
State/province [51] 0 0
Pessac
Country [52] 0 0
France
State/province [52] 0 0
Saint Priest en Jarez Cedex
Country [53] 0 0
Germany
State/province [53] 0 0
Aachen
Country [54] 0 0
Germany
State/province [54] 0 0
Bad Saarow
Country [55] 0 0
Germany
State/province [55] 0 0
Bamberg
Country [56] 0 0
Germany
State/province [56] 0 0
Dresden
Country [57] 0 0
Germany
State/province [57] 0 0
Freiburg
Country [58] 0 0
Germany
State/province [58] 0 0
Hamburg
Country [59] 0 0
Germany
State/province [59] 0 0
Koeln
Country [60] 0 0
Germany
State/province [60] 0 0
Muenchen
Country [61] 0 0
Greece
State/province [61] 0 0
GR
Country [62] 0 0
Greece
State/province [62] 0 0
Athens
Country [63] 0 0
Greece
State/province [63] 0 0
Heraklion Crete
Country [64] 0 0
Hong Kong
State/province [64] 0 0
Hong Kong
Country [65] 0 0
Hungary
State/province [65] 0 0
Budapest
Country [66] 0 0
Hungary
State/province [66] 0 0
Gyor
Country [67] 0 0
Hungary
State/province [67] 0 0
Kaposvar
Country [68] 0 0
Hungary
State/province [68] 0 0
Pecs
Country [69] 0 0
Hungary
State/province [69] 0 0
Szeged
Country [70] 0 0
Israel
State/province [70] 0 0
Haifa
Country [71] 0 0
Israel
State/province [71] 0 0
Jerusalem
Country [72] 0 0
Israel
State/province [72] 0 0
Petach Tikva
Country [73] 0 0
Israel
State/province [73] 0 0
Ramat Gan
Country [74] 0 0
Israel
State/province [74] 0 0
Tel Aviv
Country [75] 0 0
Italy
State/province [75] 0 0
BR
Country [76] 0 0
Italy
State/province [76] 0 0
CT
Country [77] 0 0
Italy
State/province [77] 0 0
FG
Country [78] 0 0
Italy
State/province [78] 0 0
FI
Country [79] 0 0
Italy
State/province [79] 0 0
GE
Country [80] 0 0
Italy
State/province [80] 0 0
LE
Country [81] 0 0
Italy
State/province [81] 0 0
MI
Country [82] 0 0
Italy
State/province [82] 0 0
MO
Country [83] 0 0
Italy
State/province [83] 0 0
PA
Country [84] 0 0
Italy
State/province [84] 0 0
PC
Country [85] 0 0
Italy
State/province [85] 0 0
PE
Country [86] 0 0
Italy
State/province [86] 0 0
PI
Country [87] 0 0
Italy
State/province [87] 0 0
PZ
Country [88] 0 0
Italy
State/province [88] 0 0
RC
Country [89] 0 0
Italy
State/province [89] 0 0
RE
Country [90] 0 0
Italy
State/province [90] 0 0
SI
Country [91] 0 0
Italy
State/province [91] 0 0
VE
Country [92] 0 0
Japan
State/province [92] 0 0
Aichi
Country [93] 0 0
Japan
State/province [93] 0 0
Chiba
Country [94] 0 0
Japan
State/province [94] 0 0
Ehime
Country [95] 0 0
Japan
State/province [95] 0 0
Hiroshima
Country [96] 0 0
Japan
State/province [96] 0 0
Ishikawa
Country [97] 0 0
Japan
State/province [97] 0 0
Kyoto
Country [98] 0 0
Japan
State/province [98] 0 0
Miyagi
Country [99] 0 0
Japan
State/province [99] 0 0
Osaka
Country [100] 0 0
Japan
State/province [100] 0 0
Shizuoka
Country [101] 0 0
Japan
State/province [101] 0 0
Tokyo
Country [102] 0 0
Japan
State/province [102] 0 0
Fukuoka
Country [103] 0 0
Japan
State/province [103] 0 0
Shinjuku-ku
Country [104] 0 0
Korea, Republic of
State/province [104] 0 0
Korea
Country [105] 0 0
Lebanon
State/province [105] 0 0
Beirut
Country [106] 0 0
Lebanon
State/province [106] 0 0
Saida
Country [107] 0 0
Mexico
State/province [107] 0 0
Distrito Federal
Country [108] 0 0
Mexico
State/province [108] 0 0
Nuevo Leon
Country [109] 0 0
New Zealand
State/province [109] 0 0
Auckland
Country [110] 0 0
New Zealand
State/province [110] 0 0
Wellington
Country [111] 0 0
Norway
State/province [111] 0 0
Oslo
Country [112] 0 0
Peru
State/province [112] 0 0
Lima
Country [113] 0 0
Poland
State/province [113] 0 0
Lubelskie
Country [114] 0 0
Poland
State/province [114] 0 0
Bydgoszcz
Country [115] 0 0
Poland
State/province [115] 0 0
Lodz
Country [116] 0 0
Poland
State/province [116] 0 0
Warsaw
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Moscow
Country [118] 0 0
Russian Federation
State/province [118] 0 0
N. Novgorod
Country [119] 0 0
Russian Federation
State/province [119] 0 0
Petrozavodsk
Country [120] 0 0
Russian Federation
State/province [120] 0 0
Saint Petersburg
Country [121] 0 0
Russian Federation
State/province [121] 0 0
St Petersburg
Country [122] 0 0
Russian Federation
State/province [122] 0 0
St. Petersburg
Country [123] 0 0
Saudi Arabia
State/province [123] 0 0
Dammam
Country [124] 0 0
Saudi Arabia
State/province [124] 0 0
Jeddah
Country [125] 0 0
Saudi Arabia
State/province [125] 0 0
Riyadh
Country [126] 0 0
Singapore
State/province [126] 0 0
Singapore
Country [127] 0 0
Slovakia
State/province [127] 0 0
Bratislava
Country [128] 0 0
Spain
State/province [128] 0 0
Andalucia
Country [129] 0 0
Spain
State/province [129] 0 0
Andalucía
Country [130] 0 0
Spain
State/province [130] 0 0
Barcelona
Country [131] 0 0
Spain
State/province [131] 0 0
Cantabria
Country [132] 0 0
Spain
State/province [132] 0 0
Catalunya
Country [133] 0 0
Spain
State/province [133] 0 0
Cataluña
Country [134] 0 0
Spain
State/province [134] 0 0
Comunidad Valenciana
Country [135] 0 0
Spain
State/province [135] 0 0
Madrid
Country [136] 0 0
Spain
State/province [136] 0 0
Navarra
Country [137] 0 0
Spain
State/province [137] 0 0
Pais Vasco
Country [138] 0 0
Switzerland
State/province [138] 0 0
CH
Country [139] 0 0
Switzerland
State/province [139] 0 0
Bellinzona
Country [140] 0 0
Thailand
State/province [140] 0 0
Bangkok
Country [141] 0 0
Thailand
State/province [141] 0 0
Songkla
Country [142] 0 0
Turkey
State/province [142] 0 0
Ankara
Country [143] 0 0
Turkey
State/province [143] 0 0
Antalya
Country [144] 0 0
Turkey
State/province [144] 0 0
Istanbul
Country [145] 0 0
Turkey
State/province [145] 0 0
Talas / Kayseri
Country [146] 0 0
Venezuela
State/province [146] 0 0
Distrito Capital

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT00790036