Simvastatin in Overcoming Chemotherapy Resistance in Patients With Relapsed or Refractory Multiple Myeloma

NCT02971410 | Withdrawn Early Phase 1 FDA Drug

• 4 other identifiers: IRB00040660NCI-2016-01465CCCWFU 26216P30CA012197
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies how well simvastatin works in overcoming chemotherapy resistance in patients with multiple myeloma that has come back or does not respond to treatment. Simvastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Change in free light chain ratios

  The success rate will be estimated overall and within the strata groups and 95% confidence intervals will be calculated around the estimate. Will also estimate the change in free light chain ratios and provide confidence intervals for those estimates, both overall and within groups.

  Up to 126 Days

• Change in M-protein level measured using electrophoresis

  The success rate will be estimated overall and within the strata groups and 95% confidence intervals will be calculated around the estimate. Will also estimate the change in M-proteins and provide confidence intervals for those estimates, both overall and within groups.

  Up to 126 Days

Secondary Outcomes (10)

• DOR

  Up to 28 months

• Incidence of toxicities evaluated according to National Cancer Institute CTCAE version 4.0

  Up to 28 months

• OR including stringent complete remission (CR), CR, Partial Remission (PR), and very good PR

  Up to 28 months

• Overall survival

  Up to 28 months

• PFS

  Up to 28 months

Study Arms (1)

Treatment (simvastatin)

EXPERIMENTAL

Patients receive standard of care chemotherapy for up to 3 courses and simvastatin (PO) daily 2 days before the first dose of chemotherapy for up to 2 days after the last dose of chemotherapy. Treatment with simvastatin continues in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Simvastatin

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (simvastatin)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (simvastatin)

Simvastatin DRUG

Given PO

Also known as: MK 733, Synvinolin, Zocor

Treatment (simvastatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a definitive diagnosis of multiple myeloma (using the International Myeloma Working Group Guidelines)
• Patients must meet one of the following two requirements:
• Have achieved minimal response (MR) or stable disease (SD) in current treatment regimen after receiving a minimum of two cycles
• Have a partial response but show a decrease less than 25% or an increase less than 25% in measurable disease over a two month period
• NOTE: Patients may be refractory to primary therapy or relapsed and have measurable or assessable disease; (refractory disease is defined as anything less than partial response \[PR\] or progression within 60 days of completing therapy)
• Patients with multiple myeloma must have measurable disease; measurable disease may be paraprotein in serum or urine or the presence of free light chains in serum or urine defined by one or more of the following criteria:
• Presence of serum M-protein concentration \> 1 g/dL
• Urine M-protein excretion \> 200 mg in 24-hour urine collection
• Serum free light chain concentration \>= 10 mg/dL and abnormal kappa/lambda ratio
• Urine free light chain concentration \>= 100 mg/L and abnormal kappa/lambda ratio
• If female patient with reproductive capacity: on effective means of barrier birth control during the entire duration of the treatment
• Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status of 0, 1, or 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 8 weeks
• Absolute neutrophil count \>= 500/ul
• Platelets \>= 30,000/ul

You may not qualify if:

• Patients who have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study
• Patients who have no measureable disease by serologic or urine markers (detectable disease only by bone marrow or imaging scans)
• Patients who show progressive disease or are not tolerating the current chemotherapy regimen
• Patients who were receiving simvastatin (dose \> 40 mg/day) while receiving current chemotherapy regimen for multiple myeloma
• Patients receiving any other investigational agent(s)
• Active second malignancy in the last 3 years except for non-melanoma skin cancer or carcinoma-in-situ
• History of hypersensitivity reactions attributed to simvastatin
• Patients receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, human immunodeficiency virus (HIV) protease inhibitors, gemfibrozil, posaconazole, danazol, amiodarone, diltiazem, and amlodipine
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myopathy, untreated hypothyroidism, hereditary myopathy in the family history, unstable angina pectoris, liver disease not due to multiple myeloma, cardiac arrhythmia that is symptomatic or not rate controlled, active connective tissue disease, active autoimmune disease, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are ineligible, as treatment involves unforeseeable risks to the embryo or fetus; female patients with reproductive capacity are required to use effective means of birth control during the entire duration of the treatment
• Patients who have been on a statin other than simvastatin within 2 weeks of starting treatment on current study; these include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, and rosuvastatin; if patient is on statin, will need to stop treatment 2 weeks prior to starting treatment on study

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Cesar Rodriguez

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2016
• First Posted: November 23, 2016
• Study Start: April 1, 2017
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: July 2, 2018

Record last verified: 2018-06

Locations

US (1)