Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
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.
Drug: glutamic acid
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
|Official Title:||Glutamic Acid to Decrease Vincristine Toxicity in Children With Cancer|
- Neurotoxicity as Measured by a Scored Neurologic Examination at Baseline, 5 Weeks, and 10 Weeks (if Applicable) [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]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.
- Frequency and Types of Neurotoxicity Observed [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]Frequency and types of neurotoxicity observed among those children treated with l-glutamic acid hydrochloride as compared to those who are in the placebo control group
- Ability to Receive All Scheduled Doses of Vincristine [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]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
|Study Start Date:||May 2007|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm I Glutamic Acid
Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Drug: glutamic acid
Given orally 3 times daily
Other Name: l-glutamic acid hydrochloride
Placebo Comparator: Arm II Placebo
Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Given orally 3 times daily
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00369564
|United States, Florida|
|Lee Cancer Care of Lee Memorial Health System|
|Fort Myers, Florida, United States, 33901|
|United States, Michigan|
|Butterworth Hospital at Spectrum Health|
|Grand Rapids, Michigan, United States, 49503-2560|
|United States, Minnesota|
|Children's Hospitals and Clinics of Minnesota - Minneapolis|
|Minneapolis, Minnesota, United States, 55404|
|United States, New Jersey|
|Hackensack University Medical Center Cancer Center|
|Hackensack, New Jersey, United States, 07601|
|United States, North Carolina|
|Blumenthal Cancer Center at Carolinas Medical Center|
|Charlotte, North Carolina, United States, 28232-2861|
|United States, Ohio|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 43205-2696|
|Study Chair:||Scott Bradfield, MD||Nemours Children's Clinic|
|Study Chair:||Eric Sandler, MD||Nemours Children's Clinic|
|Study Chair:||David R. Freyer, DO, MS||Wake Forest University Health Sciences|