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Recurrent Plasma Cell MyelomaPhase 1NCT03829020

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

A Phase 1 study testing Bortezomib, Metformin Hydrochloride and Nelfinavir Mesylate in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bortezomib, Metformin Hydrochloride and Nelfinavir Mesylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
17 Apr 2019to 24 Nov 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Provide written informed consent
  • Able to swallow metformin and nelfinavir tablets
  • Willingness to provide mandatory blood sample and bone marrow aspirate for research purposes
  • Willingness to return to Mayo Clinic for follow-up (during the active monitoring phase of the study)

Who cannot join

  • 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
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  • 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
  • Elevated baseline lactate level > ULN (2.3 mmol/L)
  • Any of the following recent prior anti-myeloma therapy:
  • Alkylators (e.g. melphalan, cyclophosphamide) and anthracyclines =< 14 days prior to registration
  • High dose corticosteroids (equivalent to > 10 mg of prednisone/day) and immunomodulatory drugs (thalidomide or lenalidomide) =< 7 days prior to registration
  • Monoclonal antibodies =< 14 days prior to registration
  • Currently receiving sensitive/moderate sensitive substrates of CYP3A4, strong CYP3A4 inhibitors, or strong CYP3A4 inducers that cannot be discontinued 7 days prior to starting study and throughout study therapy

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: An Open-Label Phase 1 Study of Metformin and Nelfinavir in Combination With Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the maximum tolerated dose (MTD) of administering metformin hydrochloride (metformin) and nelfinavir mesylate (nelfinavir) in combination with bortezomib in patients with relapsed/refractory multiple myeloma.

SECONDARY OBJECTIVES:

  1. To describe the safety and tolerability of metformin and nelfinavir in combination with bortezomib in patients with relapsed/refractory multiple myeloma.

II. To assess the best hematological response of the combination of metformin, nelfinavir and bortezomib within 6 cycles of initiating therapy.

EXPLORATORY OBJECTIVE:

  1. Assess clinical biomarkers predictive of response to the combination of metformin, nelfinavir and bortezomib such as bioenergetic profiles of the myeloma cells, GLUT4 expression on myeloma cells, PI3K/AKT/mTOR and MAPK signaling pathways and metabolomics-based profiling.

OUTLINE: This is a dose-escalation study of metformin hydrochloride and nelfinavir mesylate.

Patients receive metformin hydrochloride orally (PO) on days 1-14, nelfinavir mesylate PO twice daily (BID) on days 1-14, and bortezomib subcutaneously (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.

Being tested
Bortezomib, Metformin Hydrochloride, Nelfinavir Mesylate
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BortezomibDrug

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

    Given SC

  • Metformin HydrochlorideDrug

    Also called APO-Metformin, Cidophage, Dimefor, Glifage

    Given PO

  • Nelfinavir MesylateDrug

    Also called AG1343, Viracept

    Given PO

Study groups in NCT03829020
Study groupRoleWhat they receive
Treatment (metformin, nelfinavir)ExperimentalPatients 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.
Receives: Drug: Bortezomib; Drug: Metformin Hydrochloride; Drug: Nelfinavir Mesylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 42 days

Secondary outcomes (2)

  1. Incidence of adverse events

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

    Measured: Up to 2.5 years

  2. Hematologic response rate

    Defined to be a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) noted as the objective status on two consecutive evaluations. Exact binomial 95% confidence intervals for the true hematologic response rate will be calculated.

    Measured: Up to 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start17 Apr 2019
  3. Primary completion21 Sep 2022
  4. Study completion24 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829020
Sponsor's protocol ID
MC1811
Other IDs
NCI-2019-00466, MC1811, 18-000858
Status last verified
Aug 2024
First submitted
1 Feb 2019
Last updated
22 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bortezomib, Metformin Hydrochloride and Nelfinavir Mesylate in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of the combination of metformin, nelfinavir, and bortezomib (time frame: 42 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03829020.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.

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