Phase II Study of Simvastatin for Relapsed/Refractory Myeloma

NCT01332617 | Withdrawn Phase 2 DMC

• 1 other identifier: BCC-HEM-10-001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study test the hypothesis that the combination of simvastatin and zoledronic acid (for reversal of drug resistance), with bortezomib, high-dose methylprednisolone and bendamustine on a day 1,8 schedule (to reduce toxicity) will be an effective and well-tolerated treatment for relapsed and refractory multiple myeloma

Conditions

Myeloma

Keywords

Multiple Myeloma; Simvastatin; Zoledronic; Bortezomib; Bendamustine; Methylprednisolone

Outcome Measures

Primary Outcomes (1)

• Response to treatment as defined by The International Myeloma Working Group response criteria for multiple myeloma.

  Response catergories (IMWG): Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Minor Response (MR), Progressive Disease (PD), Stable Disease, Relapse,Refractory Disease, Overall Response.

  4 weeks after first dose of simvastatin

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  After 1 year of follow-up.

• Incidence Rate of Toxicity

  End of study; monitoring during study.

• Overall Survival (OS)

  After 1 year of follow-up

Study Arms (1)

Treatment with combination therapy

EXPERIMENTAL

Treatment with combination therapy of Simvastatin, Zoledronic Acid, Bortezomib, Bendamustine, and Methylprednisolone.

Drug: Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone.

Interventions

Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone. DRUG

1. Simvastatin 80 mg PO daily starting day -2 through day 10. 2. Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly 3. Bortezomib 1.3 mg/m2/day IV bolus on days 3,6 and 10. 4. Bendamustine 100 mg/m2/day IV over 30 minute infusion on days 3 and 10. 5. Methylprednisolone 1g/m2 IV over 30 minutes on days 1 and 8.

Also known as: Simvastatin (ZOCOR), Methylprednisolone (Medrol), Bortezomib (Voltarol, Diclofenac), Bendamustine (Treanda), Zoledronic acid (Zometa, Reclast, Zomera)

Treatment with combination therapy

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 diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines)
• Patients must have failed at least one prior treatment regimen containing bortezomib.
• They may be refractory to primary therapy or relapsed and have measurable or assessable disease. (Refractory disease is defined as anything less than PR or progression within 60 days of completing therapy.)
• Patients with Multiple Myeloma must have measurable active, progressive or symptomatic disease. Measurable disease may be paraprotein or free light chains in serum or urine, or the presence of bone marrow plasma cells.
• Age- must be at least 18 years of age.
• Prior therapies may include bendamustine, bortezomib, methylprednisolone, radiation, and autologous hematopoietic cell transplant.
• Patients who have received therapy must be at least 4 weeks beyond prior chemotherapy (excluding corticosteroids).
• If female patient with reproductive capacity: on effective means of birth control during the entire duration of the treatment.
• Patients must have recovered from acute toxicities resulting from therapy administered prior to entering this study to grade 1 or less. Alopecia may not be resolved.
• Ability to understand and willingness to sign a written informed consent document.
• Life expectancy of greater than 8 weeks.
• ECOG performance status 0, 1, or 2 (Karnofsky \> 60%; see Appendix A).
• Patients must have adequate bone marrow function as defined below:
• absolute neutrophil count \> 500/ul platelets \> 30,000/ul
• Patients must have adequate liver function as defined below: total bilirubin \< 2 times the upper limit of normal AST(SGOT), ALT(SGPT) \< 3 x upper limit of normal

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 were receiving simvastatin (dose \> 40 mg/day), or the equivalent dose of another statin) during last prior chemotherapy for multiple myeloma.
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients receiving any other investigational agent(s).
• Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ.
• History of hypersensitivity reactions attributed to simvastatin, bortezomib, bendamustine or zoledronic acid.
• Pregnant women are ineligible, as treatment involves unforeseeable risks to the embryo or fetus.
• Patients receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, niacin, HIV protease inhibitors.
• 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.

Sponsors & Collaborators

• University of Louisville: lead
• James Graham Brown Cancer Center: collaborator

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Multiple Myeloma

Interventions

Simvastatin; Methylprednisolone; Bortezomib; Diclofenac; Bendamustine Hydrochloride; Zoledronic Acid

Condition Hierarchy (Ancestors)

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; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Butyrates; Acids, Acyclic; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles; Azoles

Study Officials

• Geoffrey Herzig, MD

  James Graham Brown Cancer Center- University of Louisville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 11, 2011
• Study Start: April 1, 2011
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2019
• Last Updated: December 29, 2017

Record last verified: 2017-12