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

NCT ID: NCT00369564

Last Updated: 2021-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2012-11-30

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.

Conditions

Kidney Cancer; Leukemia; Lymphoma; Neurotoxicity; Peripheral Neuropathy; Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

glutamic acid

Intervention Type: DRUG

Given orally 3 times daily

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).

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given orally 3 times daily

Interventions

glutamic acid

Given orally 3 times daily

Intervention Type: DRUG

placebo

Given orally 3 times daily

Intervention Type: OTHER

Other Intervention Names

l-glutamic acid hydrochloride

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: collaborator

University of South Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Bradfield, MD

Role: STUDY_CHAIR

Nemours Children's Clinic

Eric Sandler, MD

Role: STUDY_CHAIR

Nemours Children's Clinic

David R. Freyer, DO, MS

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Locations

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Countries

United States

Other Identifiers

SCUSF 0402

Identifier Type: OTHER

Identifier Source: secondary_id

ACCL 0731

Identifier Type: OTHER

Identifier Source: secondary_id

5U10CA081920-11

Identifier Type: NIH

Identifier Source: secondary_id

View Link

SCUSF 0402

Identifier Type: -

Identifier Source: org_study_id