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

This study is currently recruiting participants.
Verified July 2012 by Novartis

First Received on November 11, 2008.  
Last Updated on July 18, 2012  
History of Changes
This Clinical Trial Sponsored By: Novartis Pharmaceuticals
Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00790036
 

Purpose for Clinical Trial

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

Condition Study Intervention Phase
Diffuse Large B-cell Lymphoma Drug: RAD001
Drug: Placebo
Phase 3

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

Resource links provided by NLM:

MedlinePlus related topics:
Lymphoma
Drug Information available for:
Sirolimus
Everolimus
Temsirolimus
Rituximab

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures For Clinical Trial:

  • 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 [ Time Frame: up to 5 years after the last patient is randomized ] [ Designated as safety issue: No ]
    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.

Secondary Outcome Measures For Clinical Trial:

  • Overall survival (OS) in patients who receive RAD001 versus patients who receive matching placebo [ Time Frame: Until 338 438 deaths are observed and after a minimum follow-up of 5 years after the last patient is randomized ] [ 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 338 438 deaths are observed and after a minimum follow-up of 5 years after the last patient is randomized ] [ 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: 687
Study Start Date: July 2009
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Experimental: RAD001 Drug: RAD001

RAD001 10 mg (two 5 mg tablets), daily for 12 months
Other Name: Everolimus
Placebo Comparator: Placebo Drug: Placebo

Placebo

  Eligibility

Ages Eligible for Study:   60 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 respons

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