Clinical trial NCT00369564: 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
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Children's Oncology Group
First posted: 2006-08-29
Enrollment: 250
Sex: ALL
Minimum age (years): 3
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Neurotoxicity as Measured by a Scored Neurologic Examination at Baseline, 5 Weeks, and 10 Weeks (if Applicable)
timeFrame: 10 weeks
Secondary outcomes:
measure: Number of Participants With Neurotoxicity Observed
timeFrame: 10 weeks
measure: Ability to Receive All Scheduled Doses of Vincristine
timeFrame: 10 weeks
measure: Types of Neurotoxicities
timeFrame: 10 Weeks
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Lee Cancer Care of Lee Memorial Health System
state: Florida
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Nemours Children's Clinic
name: Scott Bradfield, MD
role: STUDY_CHAIR
affiliation: Nemours Children's Clinic
name: Eric Sandler, MD
role: STUDY_CHAIR
affiliation: Wake Forest University Health Sciences
name: David R. Freyer, DO, MS
role: STUDY_CHAIR
References: