Clinical Trial: Everolimus and Bortezomib in Treating Patients With Relapsed or Refractory Lymphoma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 1 Trial of the Combination of Everolimus (RAD001) and Bortezomib (VELCADE) for Relapsed or Refractory Lymphoma

Brief Summary:

RATIONALE: Everolimus and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with bortezomib in treating patients with relapsed or refractory lymphoma.


Detailed Summary:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of everolimus (up to 10 mg PO daily) in combination with bortezomib in patients with relapsed/refractory indolent or mantle cell non-Hodgkin's lymphoma (NHL) including cutaneous forms, or relapsed/refractory aggressive NHL ineligible for hematopoetic stem cell transplantation

Secondary

  • Evaluate the toxicity of this combination.
  • Assess the pharmacokinetics interactions between these agents.
  • Assess the response rate and 6-month progression-free survival in treated patients.
  • Obtain preliminary data to assess associations between tumor characteristics and response to treatment. in those subjects who underwent biopsy prior to study treatment.

OUTLINE: This is a dose-escalation study.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Patients also receive oral everolimus once daily or once every other day on days 1-21 in all courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients will undergo blood sample collection on Cycle 1, Day 11 for pharmacokinetic studies. Baseline tumor expression of mTOR and NFkB -related proteins (i.e., pS6K, pAKT, and cREL) and FOXP3 is assessed by immunohistochemistry.


Sponsor: Brian Hill, MD, PhD

Current Primary Outcome: Maximum tolerated dose of everolimus in combination with bortezomib [ Time Frame: after 1 course (21 days) ]

Defined as the highest dose level at which 0 out of 3, or 1 out of 6, subjects experiences dose-limiting toxicity (DLT).


Original Primary Outcome: Maximum tolerated dose of everolimus in combination with bortezomib

Current Secondary Outcome:

  • Frequency counts and percentage of patients experiencing toxicities [ Time Frame: After 1 course (21 days) ]
    Adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
  • Pharmacokinetics [ Time Frame: after 1 course (21 days) ]
  • Response rate [ Time Frame: Every 3 courses (9 weeks) for the first 12 courses, after 5th restaging scan every 6 courses (18 weeks) until off study ]
    Response assessment will use response definitions of the International Working Group (2007 guidelines). Estimated with exact 95% confidence intervals.
  • 6-month progression-free survival [ Time Frame: 6 months ]
  • Correlation of tumor characteristics with response to treatment [ Time Frame: after one course (21 days) ]
    Exploratory analyses will be done using logistic regression to assess associations between tumor characteristics or biomarkers and response.


Original Secondary Outcome:

  • Toxicities
  • Pharmacodynamics and pharmacokinetics
  • Response rate
  • 6-month progression-free survival
  • Correlation of tumor characteristics with response to treatment


Information By: Case Comprehensive Cancer Center

Dates:
Date Received: May 2, 2008
Date Started: June 2008
Date Completion:
Last Updated: October 27, 2015
Last Verified: October 2015