Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer

Lymphoma Clinical Trial

Official title:

Glutamic Acid to Decrease Vincristine Toxicity in Children With Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00369564
• Other study ID #: SCUSF 0402
• Secondary ID: SCUSF 0402ACCL 0
• Status: Completed
• Phase: Phase 3
• Start date: May 2007
• Est. completion date: November 2012

Study information

• Verified date: September 2018
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Glutamic acid may help lessen or prevent nerve damage caused by vincristine. It is not yet known whether glutamic acid is more effective than a placebo in preventing nerve damage in patients receiving vincristine for Wilms' tumor, rhabdomyosarcoma, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying glutamic acid to see how well it works compared to a placebo in reducing nerve damage caused by vincristine in young patients receiving vincristine for Wilms' tumor, rhabdomyosarcoma, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma.

Description:

OBJECTIVES:

Primary

• Compare the effect of glutamic acid vs placebo, in terms of decreasing neurotoxicity as measured by a scored neurologic examination, in young patients undergoing vincristine-containing treatment for Wilms' tumor, rhabdomyosarcoma, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma.

Secondary

• Compare the frequency and types of neurotoxicity observed in patients treated with glutamic acid versus placebo.

• Determine if a greater proportion of patients receiving glutamic acid are able to receive 100% of their scheduled doses of vincristine versus those not treated with glutamic acid.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease and duration of planned vincristine-containing treatment (Wilms' tumor or rhabdomyosarcoma with treatment planned for ≥ 9 consecutive weeks [stratum 1] vs acute lymphoblastic leukemia or non-Hodgkin's lymphoma with treatment planned for ≥ 4 consecutive weeks [stratum 2]). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) for a total of 4 doses of vincristine or week 10 (stratum 1) for a total of 9 doses of vincristine.

• Arm II: Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) for a total of 4 doses of vincristine or week 10 (stratum 1) for a total of 9 doses of vincristine.

All patients undergo neurologic examination at baseline and at 5 weeks. Patients in stratum 1 also undergo additional neurologic examination at week 10.

PROJECTED ACCRUAL: A total of 250 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 20 Years

Eligibility

INCLUSION CRITERIA:

• Patients = 3 and < 21 years of age at the time of study registration.

• Patients newly diagnosed with Wilm's tumor and scheduled to receive at least 9 consecutive weeks of chemotherapy with a vincristine-containing regimen.

• Patients newly diagnosed with rhabdomyosarcoma and scheduled to receive at least 9 consecutive weeks of chemotherapy with a vincristine-containing regimen.

• Patients newly diagnosed with ALL and scheduled to receive 4 consecutive weeks of chemotherapy with a vincristine-containing regimen with accompanying steroid therapy.

• Patients newly diagnosed with Non- Hodgkins Lymphoma (NHL) and scheduled to receive 4 consecutive weeks of chemotherapy with a vincristine-containing regimen with accompanying steroid therapy.

• Patients with no underlying neuromuscular disease or peripheral neuropathy

EXCLUSION CRITERIA:

• Abnormal baseline peripheral neurologic exam (i.e. or peripheral neuropathy)

• Patients with:

• seizure disorders

• primary intracranial malignancy

• family history of Charcot Marie Tooth Disease

• a recent history of GuillianBarré26

• Patients receiving concomitant itraconazole are at risk for increased vincristine toxicity and therefore are ineligible.

• Patients who are regularly using laxatives or stool softeners for constipation at the time of enrollment are not eligible to participate in the study. Likewise, since prevention of neuro-constipation will be evaluated, patients with an ongoing history of constipation that has required frequent use of laxatives or stool softeners should not be enrolled.

• Patients should not be scheduled to receive laxatives or stool softeners prophylactically to prevent constipation, as the prevention of neuro-constipation will be evaluated in this study; however, when patients show signs of developing constipation while on chemotherapy, as determined by the treating physician, they may be treated with laxatives or stool softeners at the clinician's discretion. Use of laxatives or stool softeners will be documented on the concomitant medication log.

Related Conditions & MeSH terms

• Kidney Cancer
• Kidney Neoplasms
• Leukemia
• Lymphoma
• Neurotoxicity
• Neurotoxicity Syndromes
• Peripheral Nervous System Diseases
• Peripheral Neuropathy
• Sarcoma

Intervention

Drug:
• glutamic acid
Given orally 3 times daily

Other:
• placebo
Given orally 3 times daily

Locations

Country	Name	City	State
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
University of South Florida	Children's Oncology Group, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurotoxicity as Measured by a Scored Neurologic Examination at Baseline, 5 Weeks, and 10 Weeks (if Applicable)	A neurological exam will be completed at baseline and at study week 5 for both strata. An additional exam at week 10 will be done for patients in Stratum 1. Additional exams will be done at any time if the treating oncologist deems it clinically necessary . Neurotoxicity will be scored using a standardized neurological exam form developed for the study that is based on the Modified "Balis" Pediatric Scale of Peripheral Neuropathies. Treatment groups will be compared with respect to the proportion experiencing a grade 2 or higher toxicity from the following list of neurologic toxicities captured on the Neurologic Exam Form including sensory neuropathy, motor neuropathy, laryngeal nerve, constipation/neuro-constipation, jaw pain, or other specified abnormalities noted by the attending physician. Percentage of patients with one or more Grade 2 or higher noted neurotoxicity symptoms on any item in the Balis scale will compared between arms.	10 weeks
Secondary	Number of Participants With Neurotoxicity Observed	Number of participants with neurotoxicity observed treated with l-glutamic acid hydrochloride as compared to the number of participants with neurotoxicity observed in the placebo control group	10 weeks
Secondary	Ability to Receive All Scheduled Doses of Vincristine	We will determine if a greater proportion of patients receiving l-glutamic acid hydrochloride are able to receive 100% of their scheduled doses of vincristine as compared to those in the placebo control group	10 weeks
Secondary	Types of Neurotoxicities	Types of neurotoxicities reported. Each patient was only counted once for each type of neurotoxicity, but a patient could be counted in more than 1 type of neurotoxicity. For example, if a patient experienced constipation 3 times, they are included once for constipation. If a patient experienced sensory changes and motor changes, they are included once for sensory changes and once for motor changes.	10 Weeks