Glutamine in Preventing Peripheral Neuropathy in Patients With Multiple Myeloma Receiving Bortezomib

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Placebo Controlled Study to Estimate the Effect Size of Glutamine as a Supplement to Prevent Bortezomib-induced Peripheral Neuropathy in Multiple Myeloma Patients

Conditions
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Chemotherapeutic Agent Toxicity, Multiple Myeloma, Peripheral Neuropathy

Intervention / Treatment
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* Drug: glutamine
* Other: quality-of-life assessment
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (preventative nutritional supplementation)<br>Patients receive glutamine PO BID. Courses repeat every 28 days for 4 months in the absence of disease progression or unacceptable toxicity. | Drug: glutamine<br>* Dose of 15 grams twice times daily (to equal 30 grams a day) for a period of 4 months.<br>* Other names: NutreStore;Other: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO BID. Courses repeat every 28 days for 4 months in the absence of disease progression or unacceptable toxicity. | Other: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: placebo<br>* Given PO<br>* Other names: PLCB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 4 months from start of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 4 months | 
| 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. | up to 4 months from start of study | 
| 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 | from baseline to end of study at 4 months |