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 (PILLAR-2)


Tracking Information

Start Date  ICMJEJuly 2009
Estimated Primary Completion DateMay 2016   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: November 12, 2008)
  • Disease-free survival (DFS): Disease-free survival (DFS) is the time from date of randomization to the date of event defined as the first documented recurrence of the disease or death due to any cause. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of adverse events, serious adverse events, changes from baseline in vital signs and laboratory results (hematology, blood chemistry and urinalysis). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of non-infectious pneumonitis. Chest CT scans or PET/CT scans will be performed at screening, at regular intervals, as clinically indicated if there is a suspicion of non-infectious pneumonitis, and at the end of the study. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00790036 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: November 12, 2008)
  • Overall survival (OS): Overall survival 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. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Lymphoma-specific survival: Lymphoma-specific survival 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. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEPhase 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
Official Title  ICMJEA 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
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 have achieved complete response with first-line rituximab-chemotherapy

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJEPrevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Condition  ICMJEDiffuse Large B-cell Lymphoma
Intervention  ICMJE
  • Drug: RAD001
    RAD001 10 mg (two 5 mg tablets), daily for 12 months
    Other Name: Everolimus
  • Drug: Placebo
    Placebo
Study Arms / Comparison Groups
  • RAD001: Experimental
    Intervention: Drug: RAD001
  • Placebo: Placebo Comparator
    Intervention: Drug: Placebo

Recruitment Information

Estimated Enrollment  ICMJE915
Completion Date 
Estimated Primary Completion DateMay 2016   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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-CHOP treatment. Radiation therapy in combination with R-CHOP is acceptable if the radiation therapy ended by the time of R-CHOP completion. Complete remission from R-CHOP must be confirmed by clinical and radiologic evaluation along with bone marrow confirmation (if bone marrow was involved by lymphoma before the R-CHOP treatment). Local pathology report on the bone marrow biopsy is acceptable. If bone marrow was not involved by lymphoma before R-CHOP treatment, then another bone marrow confirmation after R-CHOP is not required.

Patients who received a minimum 6 cycles of R-CHOP treatment and maximum 8 cycles of R-CHOP treatment. Any variation of CHOP (R-CHOP-14, R-CHOP-21) is acceptable. Liposomal doxorubicin is acceptable.

Patients' last treatment with R-CHOP must be 6 to 12 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.

Exclusion Criteria:

Patients with evidence of disease according to the revised IWRC (Cheson et al 2007) after completion of the first-line R-CHOP treatment, prior to study entry.

Patients receiving ongoing radiation therapy or who received radiation therapy to the residual tumor masses after completing R-CHOP.

Patients who have previously received systemic mTOR inhibitor (sirolimus, temsirolimus, everolimus, etc).

Patients with evidence of current central nervous system (CNS) involvement. Patients who have only had prophylactic intrathecal or intravenous 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.

GenderBoth
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Novartis Pharmaceuticlas800-340-6843
Location Countries  ICMJEUnited States,   Argentina,   Australia,   Austria,   Brazil,   Canada,   China,   Colombia,   Czech Republic,   Egypt,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Mexico,   New Zealand,   Norway,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Thailand,   Turkey,   Venezuela

Administrative Information

NCT ID  ICMJENCT00790036
Responsible PartyExternal Affairs, Novartis Pharmaceuticals
Study ID Numbers  ICMJECRAD001N2301, EUDRACT 2008-000498-40
Study Sponsor  ICMJENovartis Pharmaceuticals
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:Novartis PharmaceuticlasNovartis Pharmaceuticals
Information Provided ByNovartis