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 - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00790036

Purpose

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	Intervention	Phase
Diffuse Large B-cell Lymphoma	Drug: RAD001 Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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: Everolimus Rituximab

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	915
Study Start Date:	July 2009
Estimated Primary Completion Date:	May 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
RAD001: Experimental	Drug: RAD001 RAD001 10 mg (two 5 mg tablets), daily for 12 months
Placebo: Placebo Comparator	Drug: Placebo Placebo

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790036

Contacts

Contact: Novartis Pharmaceuticlas

800-340-6843

Show 170 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticlas

Novartis Pharmaceuticals

More Information

Additional Information:

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Novartis Pharmaceuticals ( External Affairs )
Study ID Numbers:	CRAD001N2301, EUDRACT 2008-000498-40
Study First Received:	November 11, 2008
Last Updated:	January 12, 2010
ClinicalTrials.gov Identifier:	NCT00790036 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

Diffuse large B cell lymphoma
poor risk
R-IPI 3-5
adjuvant therapy
after R-CHOP

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Everolimus
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases

Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on February 08, 2010