Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Diferuloylmethane Derivative, Curcumin, Bioperine
Brief summary
Primary Objectives: 1. To evaluate clinical tolerance and response to curcumin alone and in combination with Bioperine in patients with multiple myeloma. 2. To compare the pharmacokinetics and pharmacodynamics of curcumin and curcumin + Bioperine and evaluate the effect of Bioperine on the bioavailability of curcumin. 3. To evaluate the biologic effects of curcumin alone and in combination with Bioperine on the expression of NF-kB and related genes in the Multiple Myeloma (MM) cells.
Detailed description
Curcumin, a yellow substance extracted from the plant Curcuma longa, is commonly used as a food additive. It is a natural anti-inflammatory compound and has shown anti-tumor activity in the laboratory. Bioperine is a pepper extract that increases the absorption of nutrient supplements. In this study, 6 patients at a time will be randomly assigned (as in the toss of a coin) to one of two groups of 3 patients each. One group (Arm A) will receive curcumin alone. The other group (Arm B) will receive curcumin in combination with Bioperine. There is an equal chance of being in either group. While on study you may receive standard supportive care as appropriate. Both of the study agents will be taken by mouth two times a day. Each group will have five dose levels of curcumin, starting with the lowest dose. After 6 patients have been enrolled in the first level (3 in each arm), the next group will be treated at a new dose level. You will always receive the same dose during your treatment, which will continue for at least 12 weeks unless there is evidence that the disease has gotten worse or intolerable side effects occur. You may receive treatment up to one year depending on your response to treatment. You may be treated as outpatient and may receive your treatment at home. You will be asked to return to M. D. Anderson every 4 weeks for evaluation and physical exam. This is an investigational study. A total of up to 30 evaluable patients will take part in the study. All will be enrolled at M. D. Anderson.
Interventions
DRUGCurcumin
2 grams (Capsules) orally in 2 divided doses (a.m., p.m.)
DRUGBioperine
5 mg (Tablets) orally twice daily
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with multiple myeloma who have been previously untreated, are asymptomatic and without serious or imminent complications; or have relapsed or failed treatment with conventional therapy. * Adequate hematologic, renal, and hepatic functions. * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
Exclusion criteria
* Previously untreated patients with high tumor mass; symptomatic or impending fractures. * Patients with significant cardiac disease. * Patients with comorbid condition which renders patients at high risk of treatment complications. * History of significant neurological or psychiatric disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change of NF-kB Protein Expression in Peripheral Blood Mononuclear Cells From Baseline Through 4 Weeks of Treatment | Baseline through 4 weeks of treatment | Percent change of NF-kB =\[(expression at 4 weeks- expression at baseline)/expression at baseline\]\*100%. Bone marrow aspirate/biopsy for expression of NF-kB and related genes/proteins markers at baseline and after 4 weeks. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: 11/2004 to 1/2008. All participants were recruited at UT MD Anderson Cancer Center.
Pre-assignment details
Of 42 patients enrolled, 9 were excluded from the trial prior to group assignment because of screen failure.
Participants by arm
| Arm | Count |
|---|---|
| Curcumin Curcumin starting dose 2 grams orally in two divided doses (a.m., p.m.) | 16 |
| Curcumin + Bioperine Curcumin starting dose 2 grams orally in 2 divided doses (a.m., p.m.) and Bioperine 5 mg orally twice daily | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression | 0 | 2 |
| Overall Study | Non-compliant | 1 | 0 |
Baseline characteristics
| Characteristic | Curcumin | Curcumin + Bioperine | Total |
|---|---|---|---|
| Age Continuous | 59 years | 62 years | 59 years |
| Region of Enrollment United States | 16 participants | 17 participants | 33 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 16 | 9 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Percent Change of NF-kB Protein Expression in Peripheral Blood Mononuclear Cells From Baseline Through 4 Weeks of Treatment
Percent change of NF-kB =\[(expression at 4 weeks- expression at baseline)/expression at baseline\]\*100%. Bone marrow aspirate/biopsy for expression of NF-kB and related genes/proteins markers at baseline and after 4 weeks.
Time frame: Baseline through 4 weeks of treatment
Population: All participants in the two arms (Curcumin versus Curcumin plus Bioperine) who received at least 4 weeks of treatment were eligible for outcome evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Curcumin | Percent Change of NF-kB Protein Expression in Peripheral Blood Mononuclear Cells From Baseline Through 4 Weeks of Treatment | 21 Percent reduction | Standard Deviation 37 |
| Curcumin + Bioperine | Percent Change of NF-kB Protein Expression in Peripheral Blood Mononuclear Cells From Baseline Through 4 Weeks of Treatment | 37 Percent reduction | Standard Deviation 25 |
p-value: 0.16t-test, 2 sided