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

Study Description

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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

Condition or disease	Intervention/treatment	Phase
Chemotherapeutic Agent Toxicity; Multiple Myeloma; Peripheral Neuropathy	Drug: glutamine; Other: quality-of-life assessment; Other: placebo	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	9 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Prevention
Official Title:	A Placebo Controlled Study to Estimate the Effect Size of Glutamine as a Supplement to Prevent Bortezomib-induced Peripheral Neuropathy in Multiple Myeloma Patients
Study Start Date :	February 2013
Actual Primary Completion Date :	November 2013
Actual Study Completion Date :	November 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 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.	Drug: glutamine; Dose of 15 grams twice times daily (to equal 30 grams a day) for a period of 4 months.; Other Names: 2-aminoglutaramic acid; Gln; glutamic acid 5-amide; L-glutamine; NutreStore Other: quality-of-life assessment; Ancillary studies; Other Name: quality of life assessment
Placebo Comparator: 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.	Other: quality-of-life assessment; Ancillary studies; Other Name: quality of life assessment Other: placebo; Given PO; Other Name: PLCB

Outcome Measures

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Primary Outcome Measures :

1. Degree of Peripheral Neuropathy (PNP) [ Time Frame: at 4 months (after 4 courses) ]
   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 Outcome Measures :

1. Adherence to bortezomib treatment [ Time Frame: At the end of every month (course) for 4 months ]
   Adherence to bortezomib treatment will be assessed by comparing cumulative body surface area adjusted doses administered during the first 4 cycles between placebo and glutamine groups.
2. RR (complete remission [sCR+CR+very good partial remission [VGPR]+partial remission [PR]) [ Time Frame: At the beginning of each month and at the end of month 4 ]
   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.
3. Quality of life [ Time Frame: At baseline and at the end of month 4 ]
   Quality of life will be measured on the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) plus the 11-item neurotoxicity sub-scale (FACT/GOG-Ntx) at the start of each cycle and after completion of the 4th cycle. Higher scores represent better quality of life.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Beth Faiman

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Beth Faiman	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Beth Faiman, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT01783522 History of Changes
Other Study ID Numbers:	CASE2A10; NCI-2011-01866 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted:	February 5, 2013
Last Update Posted:	December 12, 2013
Last Verified:	December 2013

Additional relevant MeSH terms:

Peripheral Nervous System Diseases; Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders	Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neuromuscular Diseases; Nervous System Diseases; Bortezomib; Antineoplastic Agents