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Study Summary
No. 2009-0793:.......Lymphoma......Luis E. Fayad......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2009-0793
Study Title:A randomized, double-blind, placebo-controlled, multicenter 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 rituximabchemotherapy
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Physician New Patient Referral
Name:Luis E. FayadPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:LymphomaSupported By:Novartis
Phase of Study:Phase IIIReturn
Visit:
Screening visit, every month for planned txt duration of 1 year,
end-of-treatment visit that occurs within 7 days after you stop study txt, a
28-day visit, and follow-up tumor assessments every 12 weeks of year 2, every
24 weeks of years 3 and 4.
Treatment
Agents:
RAD001Home Care:RAD001 or matching placebo will be dispensed on Day 1 of each cycle on an
outpatient basis.Patients will be provided with an adequate supply of RAD001 or
matching placebo for self-administration at home.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
NA
Description/
Intervention:
The goal of this clinical research study is to learn if Affinitor (everolimus)
can slow down the growth or prevent the cancer from coming back after
treatment. The safety of everolimus will also be studied.
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Study Objectives / Outcomes
Primary objective
1) To compare 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.

Secondary objectives
1) To compare overall survival (OS) and lymphoma-specific survival (LSS) in patients who receive RAD001 versus patients who receive matching placebo.

2) To describe the safety profile of RAD001 in comparison to the matching placebo.

Exploratory objectives (if necessary)
1) To determine the effects of RAD001 on plasma and serum angiogenic and/or lymphangiogenic markers, e.g., VEGF, basic FGF, PLGF, VEGFD, sVEGFR1, sVEGFR2, sVEGFR3.

2) To explore the potential relationship between efficacy endpoints and Cmin.

3) To explore the potential relationship between adverse events and C2h.

4) To explore the potential relationship between the change from baseline in angiogenesis markers and RAD001 exposure.

5) To explore the potential relationship between the change from baseline in angiogenesis markers and efficacy endpoints.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:06/29/2010
Study Type:Phase Iii
Recruitment Status:Open
Projected Accrual:687
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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 largest 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 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 Rchemotherapy 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 cycle 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/mm^3 (or 1.0 GI/L, SI units); Platelet count >/=100,000/mm^3 (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 (</=5 x ULN if liver involvement is present); 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 highly effective 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 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 (ZevalinŽ), 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;

13) Continuation #12) 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;

14) Continuation #13) Liver disease such as cirrhosis or decompensated liver disease.

15) 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.

16) 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: Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment.

17) Continuation #16) In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject; Combination of any two of the following (a+b or a+c, or b+c): a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception; b. Placement of an intrauterine device (IUD) or intrauterine system (IUS); c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

18) Patients who are using other investigational agents or who had received investigational drugs </= 4 weeks prior to study drug start.

19) Patients unwilling to or unable to comply with the protocol.

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Links
Registration Number: NCT00790036
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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