Lymphoma, Mantle- Cell Clinical Trial
— PILLAR-1Official 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)
| Verified date | April 2021 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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®.
| Status | Completed |
| Enrollment | 58 |
| Est. completion date | April 20, 2012 |
| Est. primary completion date | April 20, 2012 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 90 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Michigan Comprehensive Cancer Center Dept of Michigan Cancer Center | Ann Arbor | Michigan |
| United States | Georgia Health Sciences University Dept. of MCG | Augusta | Georgia |
| United States | St. Francis Cancer Research Foundation Dept.ofSt.FrancisCancerRes.(2) | Beech Grove | Indiana |
| United States | Northwestern University | Chicago | Illinois |
| United States | Bay Area Cancer Research Dept.ofBayAreaCancerResearch | Concord | California |
| United States | Baylor College of Medicine Dept. of Sammons Cancer (2) | Dallas | Texas |
| United States | University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(2) | Dallas | Texas |
| United States | City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(1) | Duarte | California |
| United States | Highlands Oncology Group DeptofHighlandsOncologyGrp(2) | Fayetteville | Arkansas |
| United States | Cancer Centers of the Carolinas CC of C -Eastside | Greenville | South Carolina |
| United States | East Carolina University BrodySchool of Medicine | Greenville | North Carolina |
| United States | Rocky Mountain Cancer Centers RMCC - Denver-Midtown | Greenwood Village | Colorado |
| United States | Hackensack University Medical Center Dept ofHackensackUniversityMC | Hackensack | New Jersey |
| United States | MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (10) | Houston | Texas |
| United States | Central Indiana Cancer Centers CICC - East (2) | Indianapolis | Indiana |
| United States | UCLA/ University of California Los Angeles Dept.of Hem/Oncology | Los Angeles | California |
| United States | Advanced Medical Specialties Medical Onc Hem | Miami | Florida |
| United States | West Virginia University/ Mary Babb Randolph Cancer Center | Morgantown | West Virginia |
| United States | Mayo Clinic - Arizona Mayo Clinic - Scottsdale | Multiple Locations | Arizona |
| United States | Vanderbilt University Medical Center, Clinical Trials Center Dept. of VUMC | Nashville | Tennessee |
| United States | New York University Medical Center NYU Cancer Institute | New York | New York |
| United States | Fox Chase Cancer Center Regulatory Contact | Philadelphia | Pennsylvania |
| United States | University of Pittsburgh Medical Center Hillman Cancer Center (4) | Pittsburgh | Pennsylvania |
| United States | Western Pennsylvania Cancer Institute /Western Penn Hospital Western Pann. Cancer Inst. | Pittsburgh | Pennsylvania |
| United States | Kaiser Permanente Northwest Dept of Kaiser Northwest (3) | Portland | Oregon |
| United States | Northwest Cancer Specialists Vancouver Cancer Center (2) | Portland | Oregon |
| United States | Mayo Clinic - Rochester Hematology | Rochester | Minnesota |
| United States | University of California Davis Cancer Center Dept. of UC Davis Cancer (4) | Sacramento | California |
| United States | Washington University School Of Medicine-Siteman Cancer Ctr Medical Oncology | Saint Louis | Missouri |
| United States | Cancer Care Northwest CC Northwest- Spokane South(3) | Spokane | Washington |
| United States | Tyler Cancer Center Dept.ofTylerCancerCtr. | Tyler | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall Response Rate (ORR) | Overall response rate was defined as the percentage of participants with a best overall disease response of complete response (CR) or partial response (PR). CR was defined as complete disappearance of all extranodal lesions. PR was defined as at least a 50% decrease in the sum of the product of diameter (SPD) of all index nodal and extranodal lesions. | From date of enrollment up to disease progression or death (approximately 3.8 years) | |
| Secondary | Disease Control Rate (DCR) | Disease Control Rate was defined as the percentage of participants with best overall disease response of CR or PR or stable disease (SD). CR was defined as complete disappearance of all extranodal lesions. PR was defined as at least a 50% decrease in SPD of all index nodal and extranodal lesions. SD was defined failure to attain the criteria needed for CR or PR and failure to fulfill the criteria for at least a 50% increase in the SPD of all index nodal and extranodal (including splenic and/or hepatic nodules) lesions, taking as reference the smallest sum of the product of the diameters of all index lesions recorded at or after baseline. | From date of start of treatment up to disease progression or death (approximately up to 3.8 years) | |
| Secondary | Duration of Response | Duration of response was defined as the time from the date of first documented disease response (CR or PR) to the date of first documented progression or death due to lymphoma. CR was defined as complete disappearance of all extranodal lesions. PR was defined as at least a 50% decrease in SPD of all index nodal and extranodal lesions. | From date of start of treatment up to disease progression or death (approximately up to 3.8 years) | |
| Secondary | Progression Free Survival (PFS) | PFS was defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. | From date of start of treatment up to disease progression or death (approximately up to 3.8 years) | |
| Secondary | Overall Survival | Overall survival was defined as the time from the date of start of study treatment to the date of death due to any cause. | From date of start of treatment up to disease progression or death (approximately up to 3.8 years) | |
| Secondary | Number of Participants With At Least One Adverse Event (AE) and Serious Adverse Event (SAE) | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. | From the start of the study and 28 days after study drug discontinuation (approximately up to 18 months) |