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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00790036
Ethics application status
Date submitted
11/11/2008
Date registered
13/11/2008
Date last updated
12/07/2017

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) - 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
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) - 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.
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) - LSS was defined as time from randomization to death as a result of lymphoma.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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LE
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MI
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MO
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PA
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PC
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Italy
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PE
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Italy
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PI
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Italy
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PZ
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Italy
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RC
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Italy
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RE
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Italy
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SI
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Italy
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VE
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Japan
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Aichi
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Chiba
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Fukuoka
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Korea
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Beirut
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Russian Federation
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St Petersburg
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Russian Federation
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St. Petersburg
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Dammam
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Saudi Arabia
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Jeddah
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Saudi Arabia
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Riyadh
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Singapore
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Singapore
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Andalucia
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Andalucía
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Barcelona
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Cantabria
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Catalunya
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Spain
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Cataluña
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Spain
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Comunidad Valenciana
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Spain
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Madrid
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Navarra
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Spain
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Pais Vasco
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Switzerland
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CH
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Switzerland
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Bellinzona
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Thailand
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Bangkok
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Thailand
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Songkla
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Istanbul
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Turkey
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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
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 website
https://clinicaltrials.gov/show/NCT00790036
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

Summary results
Other publications