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

University of South Florida

Status and phase: Completed; Phase 3

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

Treatments: Drug: glutamic acid; Other: placebo

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00369564

SCUSF 0402 (Other Identifier)

5U10CA081920-11 (U.S. NIH Grant/Contract)

ACCL 0731 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 patients

Sex: All

Ages: 3 to 20 years old

Volunteers: No 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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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250 participants in 2 patient groups, including a placebo group

Arm I Glutamic Acid

Experimental group

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).

Treatment:

Drug: glutamic acid

Arm II Placebo

Placebo Comparator group

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).

Treatment:

Other: placebo