Chemotherapeutic Agent Toxicity, Multiple Myeloma, Peripheral Neuropathy
Conditions
Brief summary
This randomized phase II trial studies glutamine in preventing peripheral neuropathy in patients with multiple myeloma who are receiving bortezomib. Glutamine may help prevent peripheral neuropathy in patients receiving chemotherapy
Detailed description
PRIMARY OBJECTIVES: I. Estimate the objective effect size of glutamine compared to placebo as a prophylactic intervention to prevent bortezomib-induced peripheral neuropathy in multiple myeloma patients 4 months after their first dose of study drug. SECONDARY OBJECTIVES: I. Estimate whether glutamine delays or prevents the onset or worsening of any neuropathy as determined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria. II. Determine if glutamine may improve adherence to bortezomib therapy. III. Assess response rate (RR) and clinical benefit response rate (CBR) according to uniform international response criteria and modified European Group for Blood and Marrow Transplantation (EBMT) criteria. IV. Determine if glutamine may improve quality of life (QOL) at 4 months. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive glutamine orally (PO) twice daily (BID). Courses repeat every 28 days for 4 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO BID. Courses repeat every 28 days for 4 months in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGglutamine
Dose of 15 grams twice times daily (to equal 30 grams a day) for a period of 4 months.
OTHERquality-of-life assessment
Ancillary studies
OTHERplacebo
Given PO
Sponsors
National Cancer Institute (NCI)
Beth Faiman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of multiple myeloma who received bortezomib at a dose of 1.3mg/m2 SQ weekly * No evidence of severe pre-existing peripheral neuropathy, NCI-CTCAE v4.03 =\< 2 * Performance status =\< 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Exclusion criteria
* Concurrent use of thalidomide, vincristine, platinum compound, or other agent known to cause significant neuropathy (concurrent lenalidomide will be allowed) * Hospitalization with clinical evidence of active infections as manifested by recurrent fevers, positive blood culture results, or requiring intravenous antibiotic therapy * Inadequate liver and renal function with liver transaminases 3x the upper limit of normal * Glomerular filtration rate (GFR) according to Cockcroft-Gault \< 30 mL/min * Uncontrolled congestive heart failure * Uncontrolled mood disorders * Fasting blood glucose \>150mg/dL or blood sugar (non-fasting) \>200mg/dL if no history of diabetes. Uncontrolled diabetes with HgA1C greater 7% with last evaluation. * Seizure disorder * Monosodium glutamate (MSG) allergy or soy allergy * Life expectancy of shorter than 3 months based on clinical laboratory parameters and the investigator's opinion * Uncorrected Vitamin B12 or folate deficiency on last evaluation. * Use of over the counter (OTC) supplements other than one multivitamin tablet a day * Women who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of Peripheral Neuropathy (PNP) | up to 4 months from start of study | The Neuropathy Impairment Score -Lower Limbs (NIS-LL) is the objective measurement of PNP symptoms. The degree of PNP will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03. The CTCAE is a 0-5 scale that assesses severity of neuropathy related to cancer therapy with higher scores meaning more symptoms A difference of 2 points between groups is considered significant. This measure will be performed at baseline and at 4 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adherence to Bortezomib Treatment | Up to 4 months | Adherence reported as a percentage based on number of doses of study drug taken divided by the expected number of doses of study drug expected to be taken for the study duration. |
| RR (Complete Remission [sCR+CR+Very Good Partial Remission [VGPR]+Partial Remission [PR]) | up to 4 months from start of study | RR (sCR+CR+VGPR+PR) according to uniform international response criteria and CBR (RR+MR according to modified EBMT criteria) will be assessed with SPEP, 24h UPEP, serum urine immunofixation, and serum free light chain assay at the start of each cycle and after completion of the 4th cycle. |
| Average Change in Quality of Life Scores From Baseline to End of Study | from baseline to end of study at 4 months | Quality of life will be measured on the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) including 26 summed items (responses 0 to 4 to equal a possible total score 0-108). Higher scores represent better quality of life. Average change in Quality of Life scores from baseline to end of study will be reported for each separate arm |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Preventative Nutritional Supplementation) Patients receive glutamine PO BID. Courses repeat every 28 days for 4 months in the absence of disease progression or unacceptable toxicity.
glutamine: Dose of 15 grams twice times daily (to equal 30 grams a day) for a period of 4 months.
quality-of-life assessment: Ancillary studies | 4 |
| Arm II (Placebo) Patients receive placebo PO BID. Courses repeat every 28 days for 4 months in the absence of disease progression or unacceptable toxicity.
quality-of-life assessment: Ancillary studies
placebo: Given PO | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Arm I (Preventative Nutritional Supplementation) | Total | Arm II (Placebo) |
|---|---|---|---|
| Age, Continuous | 54.5 years | 55 years | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 9 Participants | 5 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 | 1 Participants | 1 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 8 Participants | 5 Participants |
| Region of Enrollment United States | 4 participants | 9 participants | 5 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 4 / 5 |
| serious Total, serious adverse events | 0 / 4 | 1 / 5 |
Outcome results
Primary
Degree of Peripheral Neuropathy (PNP)
The Neuropathy Impairment Score -Lower Limbs (NIS-LL) is the objective measurement of PNP symptoms. The degree of PNP will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03. The CTCAE is a 0-5 scale that assesses severity of neuropathy related to cancer therapy with higher scores meaning more symptoms A difference of 2 points between groups is considered significant. This measure will be performed at baseline and at 4 months.
Time frame: up to 4 months from start of study
Population: All participants enrolled in study and given treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Preventative Nutritional Supplementation) | Degree of Peripheral Neuropathy (PNP) | 3.40 units on a scale | Standard Deviation 7.83 |
| Arm II (Placebo) | Degree of Peripheral Neuropathy (PNP) | 3.40 units on a scale | Standard Deviation 7.83 |
Secondary
Adherence to Bortezomib Treatment
Adherence reported as a percentage based on number of doses of study drug taken divided by the expected number of doses of study drug expected to be taken for the study duration.
Time frame: Up to 4 months
Population: All patients enrolled in study and given treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Preventative Nutritional Supplementation) | Adherence to Bortezomib Treatment | 100 % of doses taken |
| Arm II (Placebo) | Adherence to Bortezomib Treatment | 98.2 % of doses taken |
Secondary
Average Change in Quality of Life Scores From Baseline to End of Study
Quality of life will be measured on the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) including 26 summed items (responses 0 to 4 to equal a possible total score 0-108). Higher scores represent better quality of life. Average change in Quality of Life scores from baseline to end of study will be reported for each separate arm
Time frame: from baseline to end of study at 4 months
Population: All participants enrolled in study and given treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Preventative Nutritional Supplementation) | Average Change in Quality of Life Scores From Baseline to End of Study | -7.5 score on a scale | Standard Deviation 4.4 |
| Arm II (Placebo) | Average Change in Quality of Life Scores From Baseline to End of Study | 3.4 score on a scale | Standard Deviation 11 |
Secondary
RR (Complete Remission [sCR+CR+Very Good Partial Remission [VGPR]+Partial Remission [PR])
RR (sCR+CR+VGPR+PR) according to uniform international response criteria and CBR (RR+MR according to modified EBMT criteria) will be assessed with SPEP, 24h UPEP, serum urine immunofixation, and serum free light chain assay at the start of each cycle and after completion of the 4th cycle.
Time frame: up to 4 months from start of study
Population: Subject data not collected due to low accrual. Research cancelled