Everolimus and Bortezomib in Treating Patients With Relapsed or Refractory Lymphoma
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|ClinicalTrials.gov Identifier: NCT00671112|
Recruitment Status : Terminated (Treatment ineffective)
First Posted : May 5, 2008
Last Update Posted : October 28, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|714leukemia Lymphoma||Drug: Bortezomib Drug: Everolimus||Phase 1|
- 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
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Trial of the Combination of Everolimus (RAD001) and Bortezomib (VELCADE) for Relapsed or Refractory Lymphoma|
|Study Start Date :||June 2008|
|Actual Primary Completion Date :||October 2015|
Experimental: Everolimus and Bortezomib
Patients will receive a combination of Everolimus by mouth and Bortezomib intravenously for a 21 day cycle.
Patients will be assigned to one of the following dose levels of Bortezomib: 0.7mg/m2, 1.0 mg/m2, or 1.3mg/m2 on days 1,4,8,11 of a 21 day cycle.
The appropriate amount of bortezomib will be drawn from the injection vial and administered as an intravenous (IV) push or sub-cutaneously over 3 to 5 seconds followed by a standard saline flush or through a running IV line.
Other Name: VelcadeDrug: Everolimus
Everolimus 5 mg PO every other day, 5 mg by mouth (PO) daily, or 10 mg PO daily
Other Name: RAD001
- 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).
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00671112
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Brian Hill, MD, PhD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|