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

NCT00369564 | Completed Phase 3 Results DMC

• 3 other identifiers: SCUSF 0402ACCL 07315U10CA081920-11
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 6

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants With Neurotoxicity Observed

  10 weeks

• Ability to Receive All Scheduled Doses of Vincristine

  10 weeks

• Types of Neurotoxicities

  10 Weeks

Study Arms (2)

Arm I Glutamic Acid

EXPERIMENTAL

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

Arm II Placebo

PLACEBO COMPARATOR

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

Interventions

glutamic acid DRUG

Given orally 3 times daily

Also known as: l-glutamic acid hydrochloride

Arm I Glutamic Acid

placebo OTHER

Given orally 3 times daily

Arm II Placebo

Eligibility Criteria

• Age: 3 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of South Florida: lead
• National Cancer Institute (NCI): collaborator
• Children's Oncology Group: collaborator

Study Sites (6)

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503-2560, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

MeSH Terms

Conditions

Kidney Neoplasms; Leukemia; Lymphoma; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Sarcoma; Wilms Tumor; Lymphoma, Large B-Cell, Diffuse; Dendritic Cell Sarcoma, Interdigitating; Burkitt Lymphoma

Interventions

Glutamic Acid; glutamic acid diethyl ester

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Neuromuscular Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Histiocytic Disorders, Malignant; Histiocytosis; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Excitatory Amino Acids

Results Point of Contact

• Title: Scott Bradfield, MD
• Organization: Nemours Children's Clinic

sbradfie@nemours.org

904-697-3793

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: May 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: August 11, 2021
• Results First Posted: March 14, 2014

Record last verified: 2018-09

Locations

US (6)