search
Back to results

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

Primary Purpose

Kidney Cancer, Leukemia, Lymphoma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
glutamic acid
placebo
Sponsored by
University of South Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Kidney Cancer focused on measuring 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

Eligibility Criteria

3 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Lee Cancer Care of Lee Memorial Health System
  • Butterworth Hospital at Spectrum Health
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • Hackensack University Medical Center Cancer Center
  • Blumenthal Cancer Center at Carolinas Medical Center
  • Nationwide Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I Glutamic Acid

Arm II Placebo

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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.

Full Information

First Posted
August 24, 2006
Last Updated
July 22, 2021
Sponsor
University of South Florida
Collaborators
National Cancer Institute (NCI), Children's Oncology Group
search

1. Study Identification

Unique Protocol Identification Number
NCT00369564
Brief Title
Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
Official Title
Glutamic Acid to Decrease Vincristine Toxicity in Children With Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
May 2007 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of South Florida
Collaborators
National Cancer Institute (NCI), Children's Oncology Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer, Leukemia, Lymphoma, Neurotoxicity, Peripheral Neuropathy, Sarcoma
Keywords
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

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
250 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I Glutamic Acid
Arm Type
Experimental
Arm Description
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).
Arm Title
Arm II Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
glutamic acid
Other Intervention Name(s)
l-glutamic acid hydrochloride
Intervention Description
Given orally 3 times daily
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
Given orally 3 times daily
Primary Outcome Measure Information:
Title
Neurotoxicity as Measured by a Scored Neurologic Examination at Baseline, 5 Weeks, and 10 Weeks (if Applicable)
Description
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.
Time Frame
10 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Neurotoxicity Observed
Description
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
Time Frame
10 weeks
Title
Ability to Receive All Scheduled Doses of Vincristine
Description
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
Time Frame
10 weeks
Title
Types of Neurotoxicities
Description
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.
Time Frame
10 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Bradfield, MD
Organizational Affiliation
Nemours Children's Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Eric Sandler, MD
Organizational Affiliation
Nemours Children's Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
David R. Freyer, DO, MS
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Study Chair
Facility Information:
Facility Name
Lee Cancer Care of Lee Memorial Health System
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Butterworth Hospital at Spectrum Health
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503-2560
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota - Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Hackensack University Medical Center Cancer Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Blumenthal Cancer Center at Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28232-2861
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205-2696
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs