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

• Sponsor: Beth Faiman (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01783522
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 9
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 1

Study Details

Study Description

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:

1. 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:

1. 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.

2. Determine if glutamine may improve adherence to bortezomib therapy.

3. 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.

4. 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

• Study Type: Interventional
• 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: Feb 1, 2013
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

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 Names: 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 Names: quality of life assessment ; Other: placebo; Given PO; Other Names: PLCB

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Beth Faiman, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01783522
• Other Study ID Numbers: CASE2A10; NCI-2011-01866
• First Posted: Feb 5, 2013
• Last Update Posted: Oct 22, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Peripheral Nervous System Diseases

Study Results

Participant Flow

Arm/Group Title	Arm I (Preventative Nutritional Supplementation)	Arm II (Placebo)
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	4	5
COMPLETED	4	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Preventative Nutritional Supplementation)	Arm II (Placebo)	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	4	5	9
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54.5	64	55
Sex: Female, Male (Count of Participants)
Female	1 25%	2 40%	3 33.3%
Male	3 75%	3 60%	6 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	5 100%	9 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 25%	0 0%	1 11.1%
White	3 75%	5 100%	8 88.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	5 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Degree of Peripheral Neuropathy (PNP)
Description	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

Outcome Measure Data

Analysis Population Description

All participants enrolled in study and given treatment.

Arm/Group Title	Arm I (Preventative Nutritional Supplementation)	Arm II (Placebo)
Arm/Group Description	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	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
Measure Participants	4	5
Mean (Standard Deviation) [units on a scale]	3.40 (7.83)	3.40 (7.83)

2. Secondary Outcome

Title	Adherence to Bortezomib Treatment
Description	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

Outcome Measure Data

Analysis Population Description

All patients enrolled in study and given treatment

Arm/Group Title	Arm I (Preventative Nutritional Supplementation)	Arm II (Placebo)
Arm/Group Description	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	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
Measure Participants	4	5
Number [% of doses taken]	100	98.2

3. Secondary Outcome

Title	RR (Complete Remission [sCR+CR+Very Good Partial Remission [VGPR]+Partial Remission [PR])
Description	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

Outcome Measure Data

Analysis Population Description

Subject data not collected due to low accrual. Research cancelled

Arm/Group Title	Arm I (Preventative Nutritional Supplementation)	Arm II (Placebo)
Arm/Group Description	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	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
Measure Participants	0	0

4. Secondary Outcome

Title	Average Change in Quality of Life Scores From Baseline to End of Study
Description	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

Outcome Measure Data

Analysis Population Description

All participants enrolled in study and given treatment.

Arm/Group Title	Arm I (Preventative Nutritional Supplementation)	Arm II (Placebo)
Arm/Group Description	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	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
Measure Participants	4	5
Mean (Standard Deviation) [score on a scale]	-7.5 (4.4)	3.4 (11.0)

Adverse Events

Time Frame	Adverse event data was collected for 21 months
Arm/Group Title	Arm I (Preventative Nutritional Supplementation)		Arm II (Placebo)
Arm/Group Description	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		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
All Cause Mortality
	Arm I (Preventative Nutritional Supplementation)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Preventative Nutritional Supplementation)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		1/5 (20%)
General disorders
Chills	0/4 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Preventative Nutritional Supplementation)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		4/5 (80%)
Eye disorders
Blurred Vision	0/4 (0%)	0	1/5 (20%)	1
Gastrointestinal disorders
Abdominal Distension	0/4 (0%)	0	1/5 (20%)	1
Constipation	0/4 (0%)	0	1/5 (20%)	2
Diarrhea	1/4 (25%)	1	1/5 (20%)	1
Flatulence	0/4 (0%)	0	1/5 (20%)	1
Gastritis	0/4 (0%)	0	1/5 (20%)	1
Gastrointestinal pain	0/4 (0%)	0	1/5 (20%)	1
Mucositis Oral	0/4 (0%)	0	1/5 (20%)	1
Nausea	1/4 (25%)	1	2/5 (40%)	5
Oral Pain	0/4 (0%)	0	1/5 (20%)	1
Toothache	0/4 (0%)	0	1/5 (20%)	1
Vomiting	0/4 (0%)	0	1/5 (20%)	2
General disorders
Fatigue	0/4 (0%)	0	1/5 (20%)	4
Fever	0/4 (0%)	0	1/5 (20%)	4
Irritability	1/4 (25%)	1	0/5 (0%)	0
Pain	0/4 (0%)	0	2/5 (40%)	4
Infections and infestations
Papulopustular rash	1/4 (25%)	1	0/5 (0%)	0
Pharyngitis	1/4 (25%)	1	0/5 (0%)	0
Injury, poisoning and procedural complications
Bruising	0/4 (0%)	0	2/5 (40%)	2
Investigations
Weight loss	1/4 (25%)	1	1/5 (20%)	1
Metabolism and nutrition disorders
Anorexia	1/4 (25%)	1	1/5 (20%)	3
Hypokalemia	1/4 (25%)	1	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	1/4 (25%)	1	1/5 (20%)	1
Bone Pain	1/4 (25%)	1	3/5 (60%)	4
Musculoskeletal and connective tissue disorders - Cramps	1/4 (25%)	1	1/5 (20%)	1
Pain in extremity	1/4 (25%)	1	0/5 (0%)	0
Nervous system disorders
Headache	1/4 (25%)	1	0/5 (0%)	0
Neuralgia	0/4 (0%)	0	1/5 (20%)	1
Paresthesia	1/4 (25%)	1	0/5 (0%)	0
Psychiatric disorders
Agitation	0/4 (0%)	0	1/5 (20%)	1
Insomnia	1/4 (25%)	1	1/5 (20%)	2
Renal and urinary disorders
Urinary retention	0/4 (0%)	0	1/5 (20%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/4 (25%)	1	0/5 (0%)	0
Skin and subcutaneous tissue disorders - eczema	0/4 (0%)	0	1/5 (20%)	1

Limitations/Caveats

This study closed early with limited accrual. Because of this, we did not collect patient data for all of the outcomes.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.