NCT02967276

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

Phase II Trial, Open Label, Clinical Activity of Metformin in Combination With High-dose of Dexamethasone (HDdexa) in Patients With Relapsed/Refractory Multiple Myeloma

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: University of Campinas, Brazil · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Phase II trial, open label, clinical activity of metformin combination with high-dose dexamethasone (HDdexa) in patients with multiple myeloma relapsed-refractory. If you are found to be eligible to take part in this study, metformin will be given continuously until completion of the treatment, disease progression, severe toxicity or intolerance. The same duration of treatment will be applied to dexamethasone. The treatment will be initiated with dexamethasone (40 mg daily for 4 days on D1-D4, D9-D12 and D17-D20) Before starting the HDDexa investigators will obtain blood and bone marrow samples for evaluation of response to the disease using biomarkers of multiple myeloma. On day 1, the patients will begin metformin XR (500mg daily with the evening meal) with gradual increase in the dose - 500 mg per week up to a maximum of 2.5 g / day if no toxicity grade ≥ 2 . Each cycle will be reset every 35 days in the 1st and 2nd cycle and every 28 days from 3rd to 6th cycle. Patients who maintained clinical response to treatment after the first cycle should use the drugs for 6 cycles, or until progression or unacceptable toxicity. Oral dexamethasone (40 mg) is administered on days 1 to 4, 9 to 12 and 17 to 20 the first and second (cycles of 35 days) and on days 1, 8, 15 and 22 of the third to sixth (cycle 28d), for a period of 190 days of treatment. Patients over 75 years will use 20 mg / day instead of 40 mg / day. Patients will be submitted to collection of tissues: blood and bone marrow to evaluate the response to disease through multiple myeloma biomarkers before the first cycle, 4th and 5th cycle of treatment to assess the response according to IMWG criteria: blood count, creatinine , calcium, lactate dehydrogenase (LDH); Beta2 microglobulin; C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR); Immunoelectrophoresis and immunofixation of the proteins in serum and urine 24 hours; 24h proteinuria; Myelogram and bone marrow biopsy (BMO) and Immunophenotyping. Clinical and laboratory exams will be conducted at the beginning and every 35 days on first 2 cycles every 28 days until the 6th cycle. Safety assessments will include history and physical examination, electrocardiography, blood count, biochemical tests (including glucose and glycated Hb) and pulse oximetry. Toxic effects will be analyzed according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4 (NCI CTCAE v4). This is an investigational study. Dexamethasone is FDA approved and commercially available for the treatment of many inflammatory diseases. Metformin is FDA approved and commercially available for the treatment of diabetes mellitus. The combination of these drugs to treat multiple myeloma is investigational. Up to 28 patients will take part in this study. This is a multicenter study, and will take place in the clinical research center at the Clinical Hematology of the Clinical Hospital, University of Campinas-UNICAMP and at the Cascavel Cancer Hospital - UOPECCAN. This study will be coordinated by the Hemocentro-UNICAMP

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Metformin XR	500 mg tablet: They take 1-5 tablets of 500 mg after dinner. Starting dose of Metformin XR 500 mg. It will have an increase of 500 mg/day each week up to the maximum tolerance from the 2500 mg / day, during the 6 cycles.
DRUG	Dexamethasone	4 mg tablet: Patients will use 40 mg per day. They take 5-10 tablets 4mg after breakfast and lunch. Patients over age 75 will use 20 mg / day.

Timeline

• Start date: 2017-01-01
• Primary completion: 2018-02-01
• Completion: 2020-02-01
• First posted: 2016-11-18
• Last updated: 2017-05-02

Locations

2 sites across 1 country: Brazil