Metformin, Nelfinavir, and Bortezomib in Treating Patients With Relapsed and/or Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT03829020|
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : October 7, 2021
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Drug: Bortezomib Drug: Metformin Hydrochloride Drug: Nelfinavir Mesylate||Phase 1|
I. 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.
I. 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.
I. 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||April 17, 2019|
|Estimated Primary Completion Date :||August 21, 2022|
|Estimated Study Completion Date :||August 21, 2022|
Experimental: Treatment (metformin, nelfinavir)
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: Metformin Hydrochloride
Drug: Nelfinavir Mesylate
- Maximum tolerated dose of the combination of metformin, nelfinavir, and bortezomib [ Time Frame: 42 days ]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).
- Incidence of adverse events [ Time Frame: Up to 2.5 years ]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.
- Hematologic response rate [ Time Frame: Up to 2.5 years ]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.
- Clinical biomarker analysis [ Time Frame: Up to 2.5 years ]Will be explored and correlated with response to the combination of metformin, nelfinavir, and bortezomib using Fisher's exact and Wilcoxon rank sum tests. Clinical biomarkers examined may include bioenergetic profiles of the myeloma cells, GLUT4 expression on myeloma cells, PI3K/AKT/mTOR and MAPK signaling pathways and metabolomics-based profiling.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829020
|United States, Minnesota|
|Mayo Clinic in Rochester||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Contact: Clincial Trials Referral Office 855-776-0015 firstname.lastname@example.org|
|Principal Investigator: Wilson I. Gonsalves, M.D.|
|Principal Investigator:||Wilson I Gonsalves||Mayo Clinic in Rochester|