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

This study has been completed.
Sponsor:
Collaborators:
Children's Oncology Group
Information provided by (Responsible Party):
University of South Florida
ClinicalTrials.gov Identifier:
NCT00369564
First received: August 24, 2006
Last updated: January 30, 2014
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Kidney Cancer
Leukemia
Lymphoma
Neurotoxicity
Peripheral Neuropathy
Sarcoma
Drug: glutamic acid
Other: placebo
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of South Florida:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 250
Study Start Date: May 2007
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Other: placebo
Given orally 3 times daily

Detailed 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.

  Eligibility

Ages Eligible for Study:   3 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369564

Locations
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
Sponsors and Collaborators
University of South Florida
Children's Oncology Group
Investigators
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 Comprehensive Cancer Center of Wake Forest University
  More Information

Additional Information:
No publications provided

Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT00369564     History of Changes
Other Study ID Numbers: SCUSF 0402, SCUSF 0402, ACCL 0731, 5U10CA081920-11
Study First Received: August 24, 2006
Results First Received: December 9, 2013
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Federal Government

Keywords provided by University of South Florida:
neurotoxicity
peripheral neuropathy
stage I Wilms tumor
stage II Wilms tumor
stage III Wilms tumor
stage IV Wilms tumor
stage V Wilms tumor
previously untreated childhood rhabdomyosarcoma
childhood grade III lymphomatoid granulomatosis
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
stage I childhood large cell lymphoma
stage II childhood large cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
childhood Burkitt lymphoma
stage I childhood small noncleaved cell lymphoma
stage II childhood small noncleaved cell lymphoma
stage III childhood small noncleaved cell lymphoma
stage IV childhood small noncleaved cell lymphoma
untreated childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Leukemia
Lymphoma
Peripheral Nervous System Diseases
Lymphoma, Non-Hodgkin
Neurotoxicity Syndromes
Sarcoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neuromuscular Diseases
Nervous System Diseases
Poisoning
Substance-Related Disorders
Neoplasms, Connective and Soft Tissue
Vincristine
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on July 28, 2014