The goal of this clinical research study is to see if Minocin® (minocycline) can help to control nerve damage that causes numbness and tingling in the hands and feet (neuropathy) in patients receiving thalidomide and/or bortezomib.

Neuropathy is one of the side effects that occurs in some patients who receive thalidomide and/or bortezomib. Usually it is mild and sometimes improves or goes away when the thalidomide or bortezomib treatment is stopped. However, in some patients, the numbness and tingling remains even after the treatment is stopped. It can make it difficult for patients to feel objects with their hands, or to feel the ground under their feet. This can lead to difficulty with tasks such as buttoning clothes or writing, as well as difficulty walking.

Minocycline is designed to help prevent inflammation of the nerves, which can stop the nerve cells from dying.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. Participants in the 2 groups will receive standard education from the study staff about the signs and symptoms of neuropathy. If you are assigned to Group A, you will take a placebo (pills that look like the study drug but do not contain any active ingredients) once on Day 1. Staring on Day 2, you will take the pills 2 times a day (every 12 hours), for 10 weeks. If you are assigned to Group B you will take a larger dose of minocycline 1 time by mouth on the day you start therapy on this study, and then a smaller dose of minocycline by mouth every 12 hours for 10 weeks. Minocycline can be taken with or without food, but it needs to be taken with liquid. No matter which group you are assigned to, you will receive thalidomide and/or bortezomib according to the standard schedule. Neither you nor your doctor nor any of the clinic or research staff will know which medication (placebo or minocycline) you are receiving. Only the pharmacist who gives you the medication will know. If there is any serious concern for your safety because of the medication you might be receiving, your doctor will be told which medication you are receiving.

Study Visits:

One (1) time a week during Weeks 1-9, you will complete the symptom questionnaire. This questionnaire may be done in person or by phone.

Before you begin each new cycle of multiple myeloma therapy for 10 weeks, the following tests and procedures will be performed:

• You will have a physical exam.
• Your complete medical history will be recorded, and you will be asked about any drugs you may be taking.
• Your performance status will be recorded.
• Blood (about 2-3 teaspoons) will be drawn for routine tests.
• Blood (about 4 teaspoons) will be drawn to test for certain cytokines.
• You will have a nerve function test.
• You will complete the questionnaire that has questions about unusual sensations you may experience in your arms, legs, hands, and feet and problems these sensations may cause for you.
• You will complete the symptom questionnaire that has questions about pain, fatigue, nausea, disturbed sleep, difficulty remembering, mood, work, and enjoyment of life.
• You will complete a questionnaire that asks about high likely you are to doze off or fall asleep while doing certain activities. This should take about 2-3 minutes.
• You will be asked about any side effects you may have experienced.

End-of-Study Visit:

Once you have completed the study medication (minocycline or placebo) after Week 10, you will be asked to return for an end-of-study visit:

• You will have a physical exam.
• Your complete medical history will be recorded, and you will be asked about any drugs you may be taking.
• Your performance status will be recorded.
• Blood (about 2-3 teaspoons) will be drawn for routine tests.
• Blood (about 4 teaspoons) will be drawn to test for certain cytokines.
• You will have a nerve function test and a neuro-cognitive test.
• You will complete the questionnaire that has questions about unusual sensations you may experience in your arms, legs, hands, and feet and problems these sensations may cause for you.
• You will complete the symptom questionnaire that has questions about pain, fatigue, nausea, disturbed sleep, difficulty remembering, mood, work, and enjoyment of life.
• You will complete a questionnaire that asks about high likely you are to doze off or fall asleep while doing certain activities. This should take about 2-3 minutes.
• You will be asked about any side effects you may have experienced.

If intolerable side effects occur, or if thalidomide and/or bortezomib for the myeloma is stopped, you will be taken off study.

This is an investigational study. Minocycline is commercially available and FDA approved for use in other diseases, such as infections caused by bacteria. Minocycline is not FDA approved for the treatment of neuropathy. In neuropathy, it is currently being used in research only. Up to 142 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Newly diagnosed English speaking patients with symptomatic multiple myeloma who have received 1 or fewer treatment cycles of thalidomide or bortezomib, and who will receive thalidomide and/or twice-weekly schedule bortezomib as part of induction therapy for their multiple myeloma
2. Age greater than or equal to 18 years
3. Able to render informed consent and to follow protocol requirements
4. Women must be postmenopausal (no menstrual period for a minimum of 1 year) or if they are of childbearing potential they must agree to use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization during the study
5. Men must agree to use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) during the study.

Exclusion Criteria:

1. Hypersensitivity to tetracyclines
2. Poorly controlled or advanced diabetes mellitus (hemoglobin A1c >/= 8 %)
3. Women who are pregnant or nursing
4. Patients with peripheral neuropathy of >/= grade 2 by CTCAE v4.0.
5. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results
6. Currently have any known malignancy other than multiple myeloma, or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence
7. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease
8. Inability to use interactive voice recognition software due to physical limitations (e.g. hearing impairment)

From the first dose through 330 days after the last dose of study medication