Clinical Activity of Metformin With High-dose of Dexamethasone in Relapse Multiple Myeloma

• Status: Unknown status
• Trial end date: 2020-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial study assessing the activity of metformin when given together with high dose of dexamethasone in treating patients with multiple myeloma (MM) that has relapse or refractory to previous treatment. High dose of dexamethasone (HDdexa) is used to treat relapse/refractary patients with myeloma and metformin also demonstrated synergistic activity with dexamethasone to eradicate MM cells in vitro and in vivo. Metformin hydrochloride, used for diabetes, may also help kill tumor cells. Giving dexamethasone with metformin may kill more MM cells and increase the response rate to HDdexa.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Campinas, Brazil
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Metformin

Criteria

Inclusion Criteria:

• Patients over 18 years;

• Multiple myeloma patients relapsed or refractory to two lines prior to treatment [at least one line using bortezomib or prior treatment with a suitable alkylating agent (at least six cycles of treatment with alkylating or progressive disease after at least two cycles of treatment with alkylating or treatment with alkylating received as part of a stem cell transplant)];

• Patients should have failed (progressive disease at or before 60 days of treatment, disease progression ≤6 months after achieving partial response or intolerance to bortezomib) to treatment with bortezomib;

• Patients with oral access to medicines;

• ECOG ≤ 2;

• Blood count: hemoglobin ≥8 g / dL; absolute neutrophil count ≥500 / mm3 and platelet count ≥30.000 / mm3, glomerular filtration rate (GFR) ≥60ml / min and adequate liver function (AST or ALT at levels 3x upper limit of normal, bilirubin in levels no greater than 2x the upper limit of normal, negative pregnancy test before study initiation or accept contraceptive use.

Exclusion Criteria:

• Patients with known hypersensitivity and / or prior therapy with metformin or its excipients;

• Diabetes mellitus who require insulin use and other oral hypoglycemic agents; patients with a history of hyperglycemia induced by steroids can be entered since HbA1C in screening visit is <8%;

• leptomeningeal or brain metastases symptomatic or untreated, or spinal cord compression;

• Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) (with the exception treated or cured chronic HBV and HCV infection, who will be allowed);

• Patients who are using another study medication or who have received drug under study for less than 4 weeks;

• It is allowed concomitant treatment with bisphosphonates; however, treatment should be started before the first dose of study therapy;

• it is not allowed to use of all herbal supplements during the study (including, but not limited to, St. John's wort, kava, None, gingko biloba, dehydroepiandrosterone [DHEA], or ginseng). megestrol acetate (Megace) or medroxyprogesterone if used as an appetite stimulant is permitted;

• Uncontrolled situations by intercurrent disease, including, but not limited to, infection ongoing and active, refractory systemic hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric / social disease that would limit compliance with the requirements of study;

• Previous Neoplasms, except skin cancer for over two years;

• Patients who are pregnant or breastfeeding.

• Any major surgery, extensive radiation therapy, chemotherapy delayed toxicity, biological therapy, chemotherapy or immunotherapy within 28 days before study.