Metformin, Nelfinavir, and Bortezomib in Treating Patients With Relapsed and/or Refractory Multiple Myeloma

NCT03829020 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: MC1811NCI-2019-0046618-000858
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of metformin and nelfinavir in combination with bortezomib in treating patients with multiple myeloma that has come back or does not respond to treatment. Metformin may stop the growth of tumor cells by disrupting the energy source within multiple myeloma cells. Nelfinavir and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving metformin, nelfinavir, and bortezomib may work better in treating patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of the combination of metformin, nelfinavir, and bortezomib

  Defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients).

  42 days

Secondary Outcomes (2)

• Incidence of adverse events

  Up to 2.5 years

• Hematologic response rate

  Up to 2.5 years

Other Outcomes (1)

• Clinical biomarker analysis

  Up to 2.5 years

Study Arms (1)

Treatment (metformin, nelfinavir)

EXPERIMENTAL

Patients receive metformin hydrochloride PO on days 1-14, nelfinavir mesylate PO BID on days 1-14, and bortezomib SC on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Drug: Metformin Hydrochloride; Drug: Nelfinavir Mesylate

Interventions

Bortezomib DRUG

Given SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (metformin, nelfinavir)

Metformin Hydrochloride DRUG

Given PO

Also known as: APO-Metformin, Cidophage, Dimefor, Glifage, Glucoformin, Glucophage, Glucophage ER, Metformin HCl, Riomet, Siofor

Treatment (metformin, nelfinavir)

Nelfinavir Mesylate DRUG

Given PO

Also known as: AG1343, Viracept

Treatment (metformin, nelfinavir)

Eligibility Criteria

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

You may qualify if:

• Actively relapsing multiple myeloma
• Measurable disease of multiple myeloma as defined by at least ONE of the following:
• Serum monoclonal protein \>= 0.5 g/dL
• If immunoglobulin A (IgA) isotype, then IgA quantification \> upper limit of normal
• \>= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• Serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Monoclonal bone marrow plasmacytosis \>= 10% (evaluable disease)
• Patients must have received at least 2 prior regimens and patients should have been exposed to a proteasome inhibitor (PI), an immunomodulatory drugs (IMiD) and an anti-CD38 antibody. NOTE: Induction therapy followed by an autologous stem cell transplant (ASCT) and maintenance therapy without any relapse counts as 1 regimen
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Hemoglobin \>= 8.0 g/dL (No red cell transfusion should have been administered within 4 days of registration) (obtained =\< 14 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to registration)
• Platelet count \>= 50,000/mm\^3 or \>= 30,000/mm\^3 if bone marrow plasma cells percentage \>= 50% by morphology (No platelet transfusion should have been administered within 7 days of registration) (obtained =\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 3 x ULN (=\< 5 x ULN for patients with liver involvement) (obtained =\< 14 days prior to registration)
• Calculated creatinine clearance \>= 45 ml/min using the Cockcroft-Gault formula (obtained =\< 14 days prior to registration)

You may not qualify if:

• The following populations should be excluded from study:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Major surgery =\< 14 days before study registration
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
• 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
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Another active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy. NOTE: Patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria
• History of myocardial infarction =\< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Known allergy to any of the study medications, their analogues or excipients in the various formulations
• Subjects must not have conditions associated with increased risk of metformin associated lactic acidosis, including New York Heart Association class III or IV congestive heart failure, history of acidosis of any type, alcoholic liver disease, or habitual intake of 3 or more alcoholic beverages per day
• Clinical history of type I or type II diabetes
• Currently on either metformin or a HIV-PI or both

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Metformin; Nelfinavir

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Wilson I. Gonsalves, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: February 4, 2019
• Study Start: April 17, 2019
• Primary Completion: September 21, 2022
• Study Completion: November 24, 2023
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

US (2)