Clinical trial NCT00702052: Safety and Efficacy of RAD001 in Participants With Mantle Cell Lymphoma Who Are Refractory or Intolerant to Velcade® Therapy
Official title: An Open-Label, Single-Arm, Phase II Study of RAD001 in Patients With Mantle Cell Lymphoma Who Are Refractory or Intolerant to Velcade® (Bortezomib)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Mantle- Cell
Keywords: Mantle Cell Lymphoma
Lymphoma
B-Cell Lymphoma
Mantle Zone Lymphoma
Refractory Lymphoma
Aggressive Lymphoma
PILLAR-1
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-06-20
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study was to evaluate the safety and efficacy of a daily, oral dose of 10 mg RAD001 in participants with Mantle Cell Lymphoma who were refractory or intolerant to Velcade® therapy and who had received at least one prior antineoplastic agent other than Velcade®, either separately or in combination with Velcade® (see inclusion criteria). Intolerance to Velcade® therapy was determined by the study investigator based on clinical evaluations. Participants were considered refractory to Velcade® if they have documented radiological progression on or within 12 months of the last dose of Velcade® when given alone or, on or within 12 months of the last dose of the last component of a combination therapy which included Velcade®.


Eligibility criteria: Inclusion Criteria:

* Adult participants (≥18 years old) with Mantle Cell Lymphoma that has been confirmed by central pathology review (archival diagnostic tumor specimen required).
* Participants with mantle cell lymphoma who have documented refractory disease to Velcade® (bortezomib) or who have documented intolerance to Velcade® therapy. Intolerance to Velcade® is determined by the study investigator based on clinical evaluations. Participants are considered refractory to Velcade® if they have documented radiological progression on or within 12 months of last dose of Velcade® when given alone or, on or within 12 months from the last dose of the last component of a combination therapy which included Velcade®. Participants are considered refractory to Velcade®, if Velcade® is part of a combination treatment for the disease.
* Participants must have received at least one prior antineoplastic agent, other than Velcade® either separately or in combination with Velcade® (bortezomib).
* At least one site of measurable nodal disease at baseline \>2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by computer tomography (CT) scan (or magnetic resonance imaging (MRI), only if CT scan can not be performed).
* Eastern Cooperative Oncology Group (ECOG) performance status = 0, 1 or 2.
* Life expectancy ≥3 months.
* Adequate bone marrow, liver and renal function.
* Platelets ≥75 x 10\^9/L (untransfused platelets).

Exclusion Criteria:

* Participants who are currently receiving anticancer therapies or have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation, antibodies, targeted therapy etc.) are not eligible.
* Previous treatment with mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus, sirolimus, temsirolimus, etc).
* Participants with prior allogeneic stem cell transplant.
* Grade 3 or 4 unresolved toxicity from prior antineoplastic therapies.
* Currently taking other investigational agents or received other investigational drugs within 4 weeks of the start of study drug.
* Participants with central nervous system (CNS) lymphoma are not eligible; head magnetic resonance imaging (MRI) (or computer tomography (CT) if MRI is not available) is required prior to study entry.
* Use of chronic, systemic corticosteroids or another immunosuppressive agent, except prednisone ≤20 mg daily (or equivalent) for adrenal insufficiency (must have been on a stable dosage regimen for ≥4 weeks prior to the first treatment with RAD001).
* HIV positive participants are not eligible; (human immunodeficiency virus (HIV) testing is not required for study entry; review of previous medical records is required).
* Uncontrolled hyperlipidemia (≥Grade 3 hyperlipidemia despite optimal supportive medical therapy).
* Active, bleeding disorders or major surgery within 4 weeks of starting study drug.
* Severe and/or uncontrolled medical conditions such as symptomatic congestive heart failure (New York Heart Association Class III or IV), unstable angina, myocardial infarction within 6 months or study start, severely impaired lung function, cirrhosis, chronic active/persistent hepatitis.
* History of another primary malignancy ≤3 years prior to study entry.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From date of enrollment up to disease progression or death (approximately 3.8 years)
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: From date of start of treatment up to disease progression or death (approximately up to 3.8 years)
measure: Duration of Response
timeFrame: From date of start of treatment up to disease progression or death (approximately up to 3.8 years)
measure: Progression Free Survival (PFS)
timeFrame: From date of start of treatment up to disease progression or death (approximately up to 3.8 years)
measure: Overall Survival
timeFrame: From date of start of treatment up to disease progression or death (approximately up to 3.8 years)
measure: Number of Participants With At Least One Adverse Event (AE) and Serious Adverse Event (SAE)
timeFrame: From the start of the study and 28 days after study drug discontinuation (approximately up to 18 months)
Other outcomes:
Locations:
city: Multiple Locations
country: United States
facility: Mayo Clinic - Arizona Mayo Clinic - Scottsdale
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group DeptofHighlandsOncologyGrp(2)
state: Arkansas
city: Concord
country: United States
facility: Bay Area Cancer Research Dept.ofBayAreaCancerResearch
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(1)
state: California
city: Los Angeles
country: United States
facility: UCLA/ University of California Los Angeles Dept.of Hem/Oncology
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center Dept. of UC Davis Cancer (4)
state: California
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers RMCC - Denver-Midtown
state: Colorado
city: Miami
country: United States
facility: Advanced Medical Specialties Medical Onc Hem
state: Florida
city: Augusta
country: United States
facility: Georgia Health Sciences University Dept. of MCG
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Cancer Research Foundation Dept.ofSt.FrancisCancerRes.(2)
state: Indiana
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers CICC - East (2)
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center Dept of Michigan Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester Hematology
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School Of Medicine-Siteman Cancer Ctr Medical Oncology
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center Dept ofHackensackUniversityMC
state: New Jersey
city: New York
country: United States
facility: New York University Medical Center NYU Cancer Institute
state: New York
city: Greenville
country: United States
facility: East Carolina University BrodySchool of Medicine
state: North Carolina
city: Portland
country: United States
facility: Northwest Cancer Specialists Vancouver Cancer Center (2)
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente Northwest Dept of Kaiser Northwest (3)
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center Regulatory Contact
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute /Western Penn Hospital Western Pann. Cancer Inst.
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Hillman Cancer Center (4)
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas CC of C -Eastside
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Clinical Trials Center Dept. of VUMC
state: Tennessee
city: Dallas
country: United States
facility: Baylor College of Medicine Dept. of Sammons Cancer (2)
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(2)
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (10)
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center Dept.ofTylerCancerCtr.
state: Texas
city: Spokane
country: United States
facility: Cancer Care Northwest CC Northwest- Spokane South(3)
state: Washington
city: Morgantown
country: United States
facility: West Virginia University/ Mary Babb Randolph Cancer Center
state: West Virginia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: