Safety and Efficacy of RAD001 in Patients With Mantle Cell Lymphoma Who Are Refractory or Intolerant to Velcade® Therapy. (PILLAR-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00702052
First received: June 19, 2008
Last updated: May 10, 2013
Last verified: May 2013
  Purpose

This study is to evaluate the safety and efficacy of a daily, oral dose of 10 mg RAD001 in patients with Mantle Cell Lymphoma who are refractory or intolerant to Velcade® therapy and who have received at least one prior antineoplastic agent other than Velcade®, either separately or in combination with Velcade® (see inclusion criteria). Intolerance to Velcade® therapy is determined by the study investigator based on clinical evaluations. Patients are 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®.


Condition Intervention Phase
Lymphoma, Mantle- Cell
Drug: RAD001
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: at the end of the study ] [ Designated as safety issue: No ]
  • Overall response rate to single-agent treatment with RAD001 in patients with mantle cell lymphoma who are refractory or intolerant to Velcade® therapy. [ Time Frame: at the end of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of Response [ Time Frame: at the end of the study ] [ Designated as safety issue: Yes ]
  • Progression Free Survival [ Time Frame: at the end of the study ] [ Designated as safety issue: Yes ]
  • Overall Survival [ Time Frame: at the end of the study ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of 10 mg daily RAD001 single-agent therapy [ Time Frame: at the end of the study ] [ Designated as safety issue: Yes ]
  • Duration of Response • Progression Free Survival • Overall Survival • Safety and tolerability of 10 mg daily RAD001 single-agent therapy [ Time Frame: at the end of the study ] [ Designated as safety issue: Yes ]

Enrollment: 58
Study Start Date: August 2008
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001 Drug: RAD001

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients (> 18 years old) with Mantle Cell Lymphoma that has been confirmed by central pathology review (archival diagnostic tumor specimen required)
  • Patients with mantle cell lymphoma who have documented refractory disease to bortezomib (Velcade®) or who have documented intolerance to Velcade® therapy. Intolerance to Velcade® is determined by the study investigator based on clinical evaluations. Patients 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®). Patients are considered refractory to Velcade®, if Velcade® is part of a combination treatment for the disease.
  • Patients must have received at least one prior antineoplastic agent, other than Velcade® either separately or in combination with bortezomib (Velcade®).
  • 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 CT scan (or MRI, only if CT scan can not be performed)
  • ECOG performance status = 0, 1 or 2
  • Life expectancy ≥ 3 months
  • Adequate bone marrow, liver and renal function
  • Platelets ≥ 75 x 109/L (untransfused platelets)

Exclusion Criteria:

  • Patients 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 mTOR inhibitors (e.g. everolimus, sirolimus, temsirolimus, etc)
  • Patients 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
  • Patients with CNS lymphoma are not eligible; head MRI (or 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 patients are not eligible; (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 (NYHA 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00702052

  Show 31 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00702052     History of Changes
Other Study ID Numbers: CRAD001N2201, 2007-005700-40
Study First Received: June 19, 2008
Last Updated: May 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Mantle Cell Lymphoma
Lymphoma
B-Cell Lymphoma
Mantle Zone Lymphoma
Refractory Lymphoma
Aggressive Lymphoma
PILLAR-1

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 22, 2014