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)
Verified May 2014 by Novartis
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
First received: November 11, 2008
Last updated: May 27, 2014
Last verified: May 2014
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
Diffuse Large B-cell Lymphoma
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
||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
Primary Outcome Measures:
Secondary Outcome Measures:
- Overall survival (OS) in patients who receive RAD001 versus patients who receive matching placebo [ Time Frame: Until 338 deaths are observed ] [ Designated as safety issue: Yes ]
OSS is defined as the time from date of randomization to date of death due to any cause. If the patient is not known to have died, survival will be censored at the date of the last contact.
- Lymphoma-specific surviva (LSS) in patients who receive RAD001 versus patients who receive matching placebo [ Time Frame: Until 338 deaths are observed ] [ Designated as safety issue: Yes ]
LSS is defined as time from randomization to death as a result of lymphoma, which means that death must be recorded as a result of lymphoma.
- Safety profile of RAD001 in comparison to the matching placebo [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Number of adverse events in patients who receive RAD001 in comparison to matching placebo.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2018 (Final data collection date for primary outcome measure)
RAD001 10 mg (two 5 mg tablets), daily for 12 months
Other Name: Everolimus
Placebo Comparator: Placebo
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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).
- 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 highly effective methods of contraception during the study and for 8 weeks after study drug administration.
- Patients who give a written informed consent obtained according to local guidelines.
- 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.
- 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
- 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.
- 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.
Female patients who are pregnant or breast feeding, or of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 8 weeks after study drug administration. Highly effective contraception methods include:
- Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study drug start.
- Patients unwilling to or unable to comply with the protocol.
Other protocol-defined inclusion/exclusion criteria may apply
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00790036
|Contact: Novartis Pharmaceuticals
|Contact: Novartis Pharmaceuticals
No publications provided
||Novartis ( Novartis Pharmaceuticals )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||November 11, 2008
||May 27, 2014
||United States: Food and Drug Administration
Keywords provided by Novartis:
Diffuse large B cell lymphoma
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 10, 2014
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Immune System Diseases
Physiological Effects of Drugs