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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 3
60 Years
80 Years
Open (Enrolling)
Diffuse Large B-cell Lymphoma

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Trial Information

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

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

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

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.

Other protocol-defined inclusion/exclusion criteria may apply

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Outcome Measure:

Disease-free Survival (DFS) in poor risk patients with DLBCL after achieving CR following first-line R-chemotherapy who receive RAD001 versus patients who receive matching placebo

Outcome Description:

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.

Outcome Time Frame:

up to 5 years after the last patient is randomized

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

February 2015

Related Keywords:

  • Diffuse Large B-Cell Lymphoma
  • Diffuse large B cell lymphoma
  • poor risk
  • R-IPI 3-5
  • adjuvant therapy
  • after R-CHOP
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse



University Hospitals of Cleveland Cleveland, Ohio  44106
Oncology Partners Network Cincinnati, Ohio  45238
Texoma Cancer Center Wichita Falls, Texas  76310
The West Clinic Memphis, Tennessee  38120
Northeast Georgia Cancer Care Athens, Georgia  30607
Advanced Medical Specialties Miami, Florida  33176
Hematology Oncology of Indiana Indianapolis, Indiana  46260
Denver Health Medical Center CACZ885M2301 Denver, Colorado  80204-4507
Northwest Cancer Specialists Vancouver Location Portland, Oregon  97210
US Oncology Central Monitoring Dallas, Texas  75246
Baylor College of Medicine Dept.of Baylor College of Med. Houston, Texas  77030
Rocky Mountain Cancer Centers RMCC - Denver-Midtown Greenwood Village, Colorado  
Georgia Health Sciences University Dept. of MCG Augusta, Georgia  30912
Ironwood Cancer and Research Centers Ironwood Chandler, Arizona  85224
Highlands Oncology Group Dept of Highlands Oncology Grp Fayetteville, Arkansas  72703
Sutter Health Cancer Research Group California Cancer Care Greenbrae, California  94904
University of California San Diego Dept of Moores Cancer Ctr (3) La Jolla, California  92093-0658
USC/Kenneth Norris Comprehensive Cancer Center Dept.ofNorrisMedicalCenter(4) Los Angeles, California  90033
Palo Alto Medical Foundation Hematology/Oncology Mountain View, California  94040
California Pacific Medical Center Medical Research Institute San Francisco, California  94120-7999
Redwood Regional Medical Group - Santa Rosa Dept. of RRMG (2) Santa Rosa, California  94503
Stanford University Medical Center Dept. of Stanford University Stanford, California  94304
Memorial Cancer Medicine Specialists Colorado Springs, Colorado  80909
Hartford Hospital Cancer Clin Research Office Hartford, Connecticut  06102
University Cancer Institute Boyton Beach, Florida  33426
Cancer Centers of Florida PA Cancer Centers of FL-Ocoee (2) Ocoee, Florida  *see dep*
Hematology Oncology Associates of Treasure Coast Hematology Onc of the Treasure Port Lucie, Florida  34952
Columbus Regional Columbus, Georgia  31904
Straub Clinic & Hospital Straub Clinic & Hospital (3) Honolulu, Hawaii  96813
Northwestern University Northwest Chicago, Illinois  60611
Rush University Medical Center Div. of Hematology & Oncology Chicago, Illinois  60612
Loyola University Medical Center /Cardinal Bernardin Cancer Loyola University (rm 101) Maywood, Illinois  60153
Indiana University Health Goshen Center for Cancer IU Cancer Center Indianapolis, Indiana  46202
University of Kansas Cancer Center Univ of Kansas (2) Kansas City, Kansas  66160
Kentuckiana Cancer Institute Kentuckiana Louisville, Kentucky  40202
Tulane University Health Sciences Center Office of Clinical Research New Orleans, Louisiana  70112
Lahey Clinic Dept of Lahey Clinic (3) Burlington, Massachusetts  01805
Mayo Clinic - Rochester Dept. of MayoClinic-Rochester Rochester, Minnesota  55905
North Mississippi Hematology /Oncology MS Hem & Onc Tupelo, Mississippi  38801
Washington University School Of Medicine-Siteman Cancer Ctr Div. of Medical Oncology St. Louis, Missouri  63110
Nevada Cancer Institute Dept. of Nevada Cancer (3) Las Vegas, Nevada  89135
Dartmouth Hitchcock Medical Center Dartmouth Lebanon, New Hampshire  03756
Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2) Morristown, New Jersey  07962
University of New Mexico Cancer Center CancerResearch & Treatment (2) Albuquerque, New Mexico  87131
Arena Oncology Associates, PC Dept.ofArenaOncologyAssoc(2) Lake Success, New York  11042
Cancer Care of Western North Carolina, PA Asheville, North Carolina  28801
Levine Cancer Institute Oncology Charlotte, North Carolina  28203
Wake Forest University Baptist Medical Center Dept. of WFUHS Winston-Salem, North Carolina  27157
Zangmeister Center / Mid Ohio Oncology/Hematology Mid Ohio Onc Hem (2) Columbus, Ohio  43219
Penn State University / Milton S. Hershey Medical Center Dept.ofMiltonS.HersheyMedCtr. Hershey, Pennsylvania  17033-0850
Allegheny General Hospital Dept.ofAlleghenyCancerCtr (2) Pittsburgh, Pennsylvania  15212
Medical University of South Carolina MUSC/HCC (2) Charleston, South Carolina  29425
Cancer Centers of the Carolinas Cancer Centers of Carolinas (3 Greenville, South Carolina  29605
Low Country Hematology Oncology Dept of Lowcountry Hem/Onc Mt. Pleasant, South Carolina  29464
University Oncology and Hematology Associates, PLLC Chattanooga, Tennessee  37403
Family Cancer Center, PLC Family Cancer Center Collierville, Tennessee  38017
University of Tennessee Cancer Institute SC-2 Memphis, Tennessee  38104
Texas Oncology, P.A. Sammons Cancer Ctr. Dallas, Texas  75251
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD Fort Worth, Texas  76104
University of Texas, Houston Medical School UT Physicians Oncology Houston, Texas  77030
MD Anderson Cancer Center/University of Texas Dept of MD Anderson (18) Houston, Texas  77030-4009
South Texas Oncology and Hematology, PA South Texas Oncology (2) San Antonio, Texas  78258
Texas A&M HealthSciencesCtr-Scott & White Memorial Hospital CenterForCancerPrevention&Care Temple, Texas  76508
University of Vermont Office of Clinical Trials Res. Burlington, Vermont  05404
Blue Ridge Research Center at Roanoke Neurological Center SC Roanoke, Virginia  24014
Dean Health System Madison, Wisconsin  53717
Waukesha Memorial Hospital Cancer Center Dept.ofWaukeshaMemorialHosp. Waukesha, Wisconsin  53188
St. Agnes Hospital SC Baltimore, Maryland  21229
University of Pittsburgh Medical Center SC-3 Pittsburgh, Pennsylvania  
University of Virginia Health Systems SC-2 Charlottesville, Virginia  22908-0334