Phase II Study of Atorvastatin Safety and Antitumor Effects in Non-Hodgkin's Lymphoma

Official Title: “A Phase II Study of Atorvastatin in Patients With Low Grade or Refractory Non-Hodgkin's Lymphoma”

The purpose of this study is to:

1. Determine changes in levels of tumor bioactivity upon treatment with atorvastatin.

Secondary objective:

2. Determine validity of tumor bioactivity as a biologic endpoint by correlation with clinical response.

3. Determine whether administration of atorvastatin is tolerable and safe in low grade NHL patients. We do not anticipate any significant toxicity since this dose of atorvastatin has been FDA approved for patients with hypercholesterolemia.

Intervention(s) in this Clinical Trial

• Drug: Atorvastatin
  • 80 mg orally once daily
• Procedure: CT scan of chest/abdomen/pelvis
  • chest/abdomen/pelvis for routine 3 month standard of care for SLL/MZL

Primary Measures

• Determine changes in levels of tumor bioactivity upon treatment with atorvastatin.
  • Time Frame: Endpoint is assessed every 3 months, up to 1 year after starting atorvastatin treatment. Fine needle aspirate and blood samples are batched and analyzed within 1 year of obtaining each sample endpoint.
    Safety Issue?: No

Secondary Measures

• Determine validity of tumor bioactivity as a biologic endpoint by correlation with clinical response.
  • Time Frame: Endpoint is assessed every 3 months, up to 1 year after starting atorvastatin treatment.
    Safety Issue?: No
• Determine whether administration of atorvastatin is tolerable and safe in low grade NHL patients. We do not anticipate any significant toxicity since this dose of atorvastatin has been FDA approved for patients with hypercholesterolemia.
  • Time Frame: Endpoint is assessed every 3 months, up to 1 year after starting atorvastatin treatment.
    Safety Issue?: Yes

Inclusion Criteria:

• >18 years old
• Disease criteria: Confirmed by Stanford Pathology to be one of the following

Non-Hodgkin's Lymphoma subtypes:

• Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL)
• Extranodal marginal zone B-cell lymphoma
• Nodal marginal zone B-cell lymphoma
• Splenic marginal zone B-cell lymphoma
• Treatment criteria
• Untreated: watchful waiting currently appropriate (includes CLL stage 0) o OR
• Prior treatment: watchful waiting currently appropriate o OR
• Refractory disease
• Staging within 4 weeks prior to enrollment (SLL, marginal zone lymphoma)
• CT chest (date)
• CT abdomen (date)
• CT pelvis (date)

OR

• Staging within 4 weeks prior to enrollment (CLL: CT not required)
• Total White Cell Count (WBC) (Value) (date)
• Absolute Lymphoma Cell Count (ALC) (Value) (date)
• Measurable disease
• 1. (Site)
• 2. (Size) OR
• CLL (only): Elevated Absolute Lymphoma Cell Count
• Disease amenable to biopsy (must check at least one): Li circulating tumor cells
• Li positive bone marrow
• Li palpable involved site (such as lymph node) measuring >1.5 cm
• ECOG performance status <2 (Karnofsky >60)
• o Status score:
• Life expectancy of greater than 3 months
• Patients must have adequate organ and marrow function (EACH must checked "yes") (Date)
• 1. Li absolute neutrophil count >1 ,000/uL
• 2. Li platelets >30,000/uL
• 3. Li total bilirubin within normal institutional limits
• 4. Li AST(SGOT) <2.5 X institutional upper limit of normal
• 5. Li ALT(SGPT) <2.5 X institutional upper limit of normal
• 6. Li creatinine within normal institutional limits OR creatinine clearance >60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential must have negative BetaHCG at enrollment

Exclusion Criteria:

• Patient has had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Patient has not recovered from adverse events due to agents administered more than four weeks earlier
• Patient with stable low grade lymphoma has had rituximab within 3 months Patient with relapsed or refractory disease has had rituximab within 1 month
• Patient has not recovered from adverse events due to surgery performed 4 weeks earlier
• Patient is receiving any other investigational agent. Known brain metastases
• Patient has taken any statin within the past 6 months prior to enrollment in the trial
• Patient currently abuses alcohol
• Patient currently takes cyclosporin or gemfibrozil Patient has a prior history of rhabdomyolysis
• Patient as uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient is pregnant. Note: Patients are not excluded if they are breastfeeding at the time of enrollment, but breastfeeding should be discontinued if the mother is treated with atorvastatin.
• HIV-positive patients receiving combination anti-retroviral therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Stanford University Other

Overall Clinical Trial Officials and Contacts

Dean Felsher Principal Investigator Stanford University  

Overall Contact: Alice Fan, MD (650) 736-8655 afan@stanford.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00185731

Study ID Number: LYMNHL0020

ClinicalTrials.gov Identifier: NCT00185731

Health Authority: United States: Institutional Review Board