Phase 2 Study of Atorvastatin Safety and Antitumor Effects in Non-Hodgkin's Lymphoma

• ClinicalTrials.gov Identifier: NCT00185731
• Recruitment Status: Completed
• First Posted: September 16, 2005
• Results First Posted: December 2, 2017
• Last Update Posted: December 2, 2017
• Sponsor: Dean Felsher
• Collaborators: The Leukemia and Lymphoma Society; Damon Runyon Cancer Research Foundation; Burroughs Wellcome
• Information provided by (Responsible Party): Dean Felsher, Stanford University

Tracking Information

• First Submitted Date: September 12, 2005
• First Posted Date: September 16, 2005
• Results First Submitted Date: January 24, 2017
• Results First Posted Date: December 2, 2017
• Last Update Posted Date: December 2, 2017
• Study Start Date: April 2005
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2017)

Tumor Apoptosis [ Time Frame: 1 year ]

Expressed as the number of participants whose tumor cells showed an increase in apoptosis during atorvastatin treatment

• Original Primary Outcome Measures (submitted: September 12, 2005): Determine changes in levels of tumor bioactivity upon treatment with atorvastatin.

Current Secondary Outcome Measures (submitted: October 25, 2017)

• Correlation of Tumor Apoptosis to Clinical Response [ Time Frame: 1 year ]
  The validity of tumor apoptosis as a biologic endpoint was assessed by correlation to clinical response. A correlation substantially less than 1 is interpreted as a poor correlation, while a correlation near +1 or -1 is interpreted as a strong correlation.
• Atorvastatin Toxicity [ Time Frame: 1 year ]
  Assessed as the number of study participants with atorvastatin-related serious adverse events (SAEs).

Original Secondary Outcome Measures (submitted: September 12, 2005)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 2 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
• Brief Summary: This is an approach which can inflict significant toxicity. An alternative is to block expression of oncogenes which are over-expressed only in cancer cells, a therapeutic approach which could reduce toxicity to the host while maximizing destruction of the oncogene-dependent malignant cells.
• Detailed Description: Atorvastatin has been shown to decrease levels of active oncogenes in preclinical studies with murine and human lymphoma cell lines, and administration of statins leads to shrinkage of lymphoma in murine models. Therefore, it may be possible for atorvastatin to decrease levels of active oncogenes in human lymphomas. Further, upon decrease in levels of active oncogenes, human lymphomas may regress. Atorvastatin is a commonly prescribed drug for hypercholesterolemia: targeting the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme may also be a way to decrease activation of oncogenes in human lymphoma, with minimal toxicity. For human low grade non-Hodgkin lymphoma, no curative treatment is available; therefore new, non-toxic and targeted therapies are sought for this disease.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Leukemia
• Lymphoma, Non-Hodgkin

Intervention

Drug: Atorvastatin

80 mg orally once daily

Other Name: Lipitor

Study Arms

Experimental: 80 mg Atorvastatin

Atorvastatin, 80 mg tablet, will be taken orally by the patient daily, beginning on study day 1.

Intervention: Drug: Atorvastatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 25, 2017): 25
• Original Enrollment (submitted: September 12, 2005): 14
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• > 18 years old

• Disease criteria: Confirmed by Stanford Pathology to be one of the following Non-Hodgkin's Lymphoma (NHL) 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 blood cell count (WBC) (Value) (date)
  • Absolute lymphoma cell count (ALC) (Value) (date)
  • Measurable disease (Site) (Size) OR
  • CLL (only): elevated absolute lymphoma cell count

• Disease amenable to biopsy (must check at least one):

  • Circulating tumor cells
  • Positive bone marrow
  • Palpable involved site (such as lymph node) measuring > 1.5 cm
• Eastern Cooperative Oncology Group performance status <2 (Karnofsky >60)
• Life expectancy of greater than 3 months

• Patients must have adequate organ and marrow function

  • Absolute neutrophil count > 1,000/uL
  • Platelets > 30,000/uL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ratio < 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m² 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:

• Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Not recovered from adverse events due to agents administered more than four weeks earlier
• Has stable low grade lymphoma has had rituximab within 3 months Patient with relapsed or refractory disease has had rituximab within 1 month
• Not recovered from adverse events due to surgery performed 4 weeks earlier
• Receiving any other investigational agent. Known brain metastases
• Taken any statin within the past 6 months prior to enrollment in the trial
• Currently abuses alcohol
• Currently takes cyclosporin or gemfibrozil Patient has a prior history of rhabdomyolysis
• Has 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.
• Pregnant: 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00185731
• Other Study ID Numbers: IRB-13683; 4328-07 ( Other Identifier: Damon Runyon Cancer Research Foundation ); 95140 ( Other Identifier: Stanford University Alternate IRB Approval Number ); LYMNHL0020 ( Other Identifier: OnCore )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Dean Felsher, Stanford University
• Study Sponsor: Dean Felsher

Collaborators

• The Leukemia and Lymphoma Society
• Damon Runyon Cancer Research Foundation
• Burroughs Wellcome

Investigators

• Principal Investigator: Dean Felsher; Stanford University

• PRS Account: Stanford University
• Verification Date: October 2017