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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 24, 2014