Glutamine in Treating Neuropathy Caused by Vincristine in Young Patients With Lymphoma, Leukemia, or Solid Tumors

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00365768
• Collaborator: (none)
• Enrollment: 56
• Location: 1
• Arms: 2
• Duration (Months): 92
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

RATIONALE: Glutamine may help lessen neuropathy caused by chemotherapy. It is not yet known whether glutamine is more effective than a placebo in treating neuropathy caused by vincristine.

PURPOSE: This randomized phase II trial is studying glutamine to see how well it works compared to a placebo in treating neuropathy caused by vincristine in young patients with lymphoma, leukemia, or solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer; Leukemia; Lymphoma; Neurotoxicity; Peripheral Neuropathy; Sarcoma	Drug: Glutamine; Other: Placebo	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the incidence of vincristine-induced peripheral neuropathy in pediatric patients with lymphoma, leukemia, or solid tumors.

Secondary

• Compare the safety of glutamine vs placebo in these patients.

• Compare the efficacy of glutamine vs placebo in reducing the progression and/or resolution of vincristine-induced peripheral neuropathy in these patients.

• Compare the effect of glutamine supplementation vs placebo on chemotherapy-related toxicities in these patients.

• Compare the effect of glutamine vs placebo on measures of quality of life in these patients.

• Compare the effect of glutamine supplementation vs placebo on serum nerve growth factor and glutamine levels in these patients.

• Determine the effect of glutamine on vincristine-mediated antitumor efficacy in vitro.

OUTLINE: This is a randomized, double-blind, placebo-controlled, pilot study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21.

• Arm II: Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21.

Patients in both arms undergo neuropsychological and clinical neurological assessment, blood collection for serum marker (e.g., serum glutamine and nerve growth factor) analysis, and quality of life assessment on days 1, 21, and 42.

After completion of study treatment, patients are followed for an additional 21 days.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Pilot Study Investigating the Effects of Glutamine and Vincristine-Induced Neuropathy in Pediatric Patients With Cancer
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I: Glutamine Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21.	Drug: Glutamine; Administered orally twice daily for 21 days; Other Names: Nutritional Supplement
Placebo Comparator: Arm II: Placebo Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21.	Other: Placebo; Administered orally twice daily for 21 days

Outcome Measures

Primary Outcome Measures

1. Incidence of Vincristine-induced Peripheral Neuropathy [Up to 30 weeks from baseline while on Vincristine treatment]

Secondary Outcome Measures

1. Number of Participants With Progression of Neuropathy [42 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients between the age of 5 and 21 years old.

• Patients who demonstrate the ability to complete the assessment instruments at baseline.

• Patients who are diagnosed with leukemia or solid tumors and are expected to receive a cumulative dose of > or = to 6mg/m2 of vincristine, or > 6mg if individual vincristine doses are capped at 2mg according to primary cancer treatment protocol, over a 30-week period.

Exclusion Criteria:

• Patients with primary CNS tumors other than medulloblastoma or patients with CNS metastasis.

• Patients with recurrent disease.

• Patients with Grade II, III or IV neurological status by the NCI CTC (Ver. 3.0) on clinical exam.

• Patients who have already received > 8mg/m2 of vincristine, or > 8mg if individual vincristine doses are capped at 2mg according to primary cancer treatment protocol, during their course of therapy at time of consent.

• Patients with hepatic encephalopathy or hyperammonemia.

• Patients with a focally abnormal neurologic exam.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University

Investigators

• Principal Investigator: Julia L. Glade-Bender, MD, Herbert Irving Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Julia Glade Bender, Irving Assistant Professor of Clinical Pediatrics, Columbia University
• ClinicalTrials.gov Identifier: NCT00365768
• Other Study ID Numbers: AAAA6806; CPMC-ICCR-3349
• First Posted: Aug 17, 2006
• Last Update Posted: Sep 9, 2016
• Last Verified: Jul 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Julia Glade Bender, Irving Assistant Professor of Clinical Pediatrics, Columbia University: stage II childhood lymphoblastic lymphoma; stage III childhood lymphoblastic lymphoma; stage II childhood small noncleaved cell lymphoma; stage I Wilms tumor; stage II Wilms tumor; stage III Wilms tumor; stage IV Wilms tumor; stage V Wilms tumor; childhood grade III lymphomatoid granulomatosis; childhood diffuse large cell lymphoma; childhood immunoblastic large cell lymphoma; stage I childhood large cell lymphoma; stage I childhood lymphoblastic lymphoma; stage I childhood small noncleaved cell lymphoma; stage II childhood large cell lymphoma; stage III childhood large cell lymphoma; stage IV childhood large cell lymphoma; stage IV childhood lymphoblastic lymphoma; stage IV childhood small noncleaved cell lymphoma; childhood Burkitt lymphoma; stage III childhood small noncleaved cell lymphoma; untreated childhood acute lymphoblastic leukemia; childhood nasal type extranodal NK/T-cell lymphoma; previously untreated childhood rhabdomyosarcoma; localized Ewing sarcoma/PNET; metastatic Ewing sarcoma/PNET; neurotoxicity; peripheral neuropathy
• Additional relevant MeSH terms: Lymphoma; Leukemia; Sarcoma; Kidney Neoplasms; Peripheral Nervous System Diseases; Neurotoxicity Syndromes

Study Results

Participant Flow

Recruitment Details	All subjects were consented according to Institutional Review Board approved guidelines during out routine outpatient or inpatient stay. The period of recruitment was from January 2007 to July 2011.
Pre-assignment Detail	Fifty-six patients were enrolled and 49 were evaluable, with the reasons for removal from study after randomization due to: change in clinical status (N=3), family withdrew (N=2), family relocation (N=1) and other (N=1). 49 patients were randomized to the glutamine or placebo arm.

Arm/Group Title	Arm I: Glutamine	Arm II: Placebo
Arm/Group Description	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21. Glutamine: Administered orally twice daily for 21 days	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21. Placebo: Administered orally twice daily for 21 days
Period Title: Overall Study
STARTED	24	25
COMPLETED	24	25
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I: Glutamine	Arm II: Placebo	Total
Arm/Group Description	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21. Glutamine: Administered orally twice daily for 21 days	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21. Placebo: Administered orally twice daily for 21 days	Total of all reporting groups
Overall Participants	24	25	49
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	11	10	11
Sex: Female, Male (Count of Participants)
Female	14 58.3%	12 48%	26 53.1%
Male	10 41.7%	13 52%	23 46.9%
Region of Enrollment (participants) [Number]
United States	24 100%	25 100%	49 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Vincristine-induced Peripheral Neuropathy
Time Frame	Up to 30 weeks from baseline while on Vincristine treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I: Glutamine	Arm II: Placebo
Arm/Group Description	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21. Glutamine: Administered orally twice daily for 21 days	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21. Placebo: Administered orally twice daily for 21 days
Measure Participants	24	25
Number [participants]	24 100%	25 100%

2. Secondary Outcome

Title	Number of Participants With Progression of Neuropathy
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I: Glutamine	Arm II: Placebo
Arm/Group Description	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21. Glutamine: Administered orally twice daily for 21 days	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21. Placebo: Administered orally twice daily for 21 days
Measure Participants	24	25
Number [participants]	11 45.8%	19 76%

Adverse Events

Arm/Group Title	Arm I: Glutamine		Arm II
Arm/Group Description	Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21. Glutamine: Administered orally twice daily for 21 days		Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21. Placebo: Administered orally twice daily for 21 days
All Cause Mortality
	Arm I: Glutamine		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I: Glutamine		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Arm I: Glutamine		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)

Limitations/Caveats

[Not Specified]

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.