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

• ClinicalTrials.gov Identifier: NCT00369564
• Recruitment Status: Completed
• First Posted: August 29, 2006
• Results First Posted: March 14, 2014
• Last Update Posted: August 11, 2021
• Sponsor: University of South Florida
• Collaborators: National Cancer Institute (NCI); Children's Oncology Group
• Information provided by (Responsible Party): University of South Florida

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.

Condition or disease	Intervention/treatment	Phase
Kidney Cancer; Leukemia; Lymphoma; Neurotoxicity; Peripheral Neuropathy; Sarcoma	Drug: glutamic acid; Other: placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Glutamic Acid to Decrease Vincristine Toxicity in Children With Cancer
• Study Start Date: May 2007
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: November 2012

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Neurotoxicity as Measured by a Scored Neurologic Examination at Baseline, 5 Weeks, and 10 Weeks (if Applicable) [ Time Frame: 10 weeks ]
   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 :

1. Number of Participants With Neurotoxicity Observed [ Time Frame: 10 weeks ]
   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
2. Ability to Receive All Scheduled Doses of Vincristine [ Time Frame: 10 weeks ]
   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
3. Types of Neurotoxicities [ Time Frame: 10 Weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 20 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

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

National Cancer Institute (NCI)

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; Wake Forest University Health Sciences

More Information

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT00369564
• Other Study ID Numbers: SCUSF 0402; SCUSF 0402 ( Other Identifier: SunCoast CCOP Research Base ); ACCL 0731 ( Other Identifier: Children's Oncology Group ); 5U10CA081920-11 ( U.S. NIH Grant/Contract )
• First Posted: August 29, 2006
• Results First Posted: March 14, 2014
• Last Update Posted: August 11, 2021
• Last Verified: September 2018

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:

Lymphoma; Kidney Neoplasms; Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuromuscular Diseases; Nervous System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Poisoning; Chemically-Induced Disorders