Myeloma
Conditions
Keywords
Multiple Myeloma, Neuropathy, Peripheral Nerve Function, Touch Detection Threshold, Nerve Damage, Thalidomide, Bortezomib, Velcade, Minocycline, Dynacin, Minocin, Minocin PAC, Myrac, Solodyn
Brief summary
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.
Detailed description
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.
Interventions
OTHERPlacebo
One pill by mouth on Day 1. Staring on Day 2, 2 times a day (every 12 hours) by mouth for 10 weeks.
DRUGMinocycline
200 mg by mouth for 1 dose, then 100 mg by mouth every 12 hours for 10 weeks.
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy. | baseline and week 10 | Touch detection thresholds are determined using the up/down method with calibrated von Frey monofilaments, Starting with a 0.5mN force, the von Frey monofilament is applied for approximately 1 sec. If the subject fails to detect the stimulus, then the next higher force von Frey monofilament is applied. When the subject detects the presence of the stimulus, the next lower von Frey is administered. The up/down test sequence continues until the same force filament is detected for three additional applications. The force of that filament is then assigned as the touch threshold |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Mean Value of Patient-reported MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM) Numbness Scores From Baseline to Week 10 Post Treatment. | baseline and week 10 | Participants reported the severity of two cognitive symptoms numbness on a 0-10 scale, with 0 being 'not present' and 10 being 'as bad as you can imagine': Higher mean scores indicate more severe symptoms. |
Countries
United States
Participant flow
Pre-assignment details
79 Participants signed consent
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group Participants received one pill by mouth on Day 1. Staring on Day 2, 2 times a day (every 12 hours) by mouth for 10 weeks. | 39 |
| Minocycline Group Participants received minocycline 200 mg orally for 1 dose, then 100 mg orally every 12 hours for 10 weeks beginning at initiation of induction therapy for multiple myeloma | 40 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 4 | 4 |
| Overall Study | Physically unable to continue | 0 | 1 |
| Overall Study | Physician Decision | 8 | 10 |
| Overall Study | Progressive disease | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo Group | Minocycline Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 13 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 27 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 36 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) White | 28 Participants | 30 Participants | 58 Participants |
| Region of Enrollment United States | 39 participants | 40 participants | 79 participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 40 |
| other Total, other adverse events | 39 / 39 | 40 / 40 |
| serious Total, serious adverse events | 15 / 39 | 12 / 40 |
Outcome results
Primary
The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy.
Touch detection thresholds are determined using the up/down method with calibrated von Frey monofilaments, Starting with a 0.5mN force, the von Frey monofilament is applied for approximately 1 sec. If the subject fails to detect the stimulus, then the next higher force von Frey monofilament is applied. When the subject detects the presence of the stimulus, the next lower von Frey is administered. The up/down test sequence continues until the same force filament is detected for three additional applications. The force of that filament is then assigned as the touch threshold
Time frame: baseline and week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Group | The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy. | Fingertips | 0.00 mN | Standard Deviation 0.25 |
| Placebo Group | The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy. | Thenar Eminence | 0.08 mN | Standard Deviation 0.26 |
| Placebo Group | The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy. | Volar Forearm | 0.09 mN | Standard Deviation 0.36 |
| Minocycline Group | The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy. | Fingertips | 0.06 mN | Standard Deviation 0.28 |
| Minocycline Group | The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy. | Thenar Eminence | 0.13 mN | Standard Deviation 0.27 |
| Minocycline Group | The Difference Between Touch Detection Thresholds From the Sensorimotor Evaluation at Baseline and After 10 Weeks of Induction Therapy. | Volar Forearm | -0.03 mN | Standard Deviation 0.44 |
Comparison: Difference in the measurements for touch by the fingertipp-value: 0.5495% CI: [-0.13, 0.24]Wilcoxon (Mann-Whitney)
Comparison: Difference in the measurements for touch by the palmp-value: 0.695% CI: [-0.13, 0.23]Wilcoxon (Mann-Whitney)
Comparison: Difference in the measurements for touch by the forearmp-value: 0.3795% CI: [-0.4, 0.15]Wilcoxon (Mann-Whitney)
Secondary
Change in the Mean Value of Patient-reported MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM) Numbness Scores From Baseline to Week 10 Post Treatment.
Participants reported the severity of two cognitive symptoms numbness on a 0-10 scale, with 0 being 'not present' and 10 being 'as bad as you can imagine': Higher mean scores indicate more severe symptoms.
Time frame: baseline and week 10
Population: Participants with quantitative sensory testing (QST) done a week prior to the start of their minocycline treatment and with corresponding QST at week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Change in the Mean Value of Patient-reported MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM) Numbness Scores From Baseline to Week 10 Post Treatment. | 1.38 score on a scale | Standard Deviation 2.36 |
| Minocycline Group | Change in the Mean Value of Patient-reported MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM) Numbness Scores From Baseline to Week 10 Post Treatment. | 0.65 score on a scale | Standard Deviation 1.79 |
Comparison: Difference in Numbness severity at baseline and week 10.p-value: 0.5695% CI: [-2.06, 0.59]Wilcoxon (Mann-Whitney)