Kidney Cancer, Leukemia, Lymphoma, Neurotoxicity, Peripheral Neuropathy, Sarcoma
Conditions
Keywords
stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage II childhood small noncleaved cell lymphoma, stage I Wilms tumor, stage II Wilms tumor, stage III Wilms tumor, stage IV Wilms tumor, stage V Wilms tumor, childhood grade III lymphomatoid granulomatosis, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, stage I childhood large cell lymphoma, stage I childhood lymphoblastic lymphoma, stage I childhood small noncleaved cell lymphoma, stage II childhood large cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood large cell lymphoma, stage IV childhood lymphoblastic lymphoma, stage IV childhood small noncleaved cell lymphoma, childhood Burkitt lymphoma, stage III childhood small noncleaved cell lymphoma, untreated childhood acute lymphoblastic leukemia, childhood nasal type extranodal NK/T-cell lymphoma, previously untreated childhood rhabdomyosarcoma, localized Ewing sarcoma/PNET, metastatic Ewing sarcoma/PNET, neurotoxicity, peripheral neuropathy
Brief summary
RATIONALE: Glutamine may help lessen neuropathy caused by chemotherapy. It is not yet known whether glutamine is more effective than a placebo in treating neuropathy caused by vincristine. PURPOSE: This randomized phase II trial is studying glutamine to see how well it works compared to a placebo in treating neuropathy caused by vincristine in young patients with lymphoma, leukemia, or solid tumors.
Detailed description
OBJECTIVES: Primary * Determine the incidence of vincristine-induced peripheral neuropathy in pediatric patients with lymphoma, leukemia, or solid tumors. Secondary * Compare the safety of glutamine vs placebo in these patients. * Compare the efficacy of glutamine vs placebo in reducing the progression and/or resolution of vincristine-induced peripheral neuropathy in these patients. * Compare the effect of glutamine supplementation vs placebo on chemotherapy-related toxicities in these patients. * Compare the effect of glutamine vs placebo on measures of quality of life in these patients. * Compare the effect of glutamine supplementation vs placebo on serum nerve growth factor and glutamine levels in these patients. * Determine the effect of glutamine on vincristine-mediated antitumor efficacy in vitro. OUTLINE: This is a randomized, double-blind, placebo-controlled, pilot study. Patients are randomized to 1 of 2 treatment arms. * Arm I: Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21. * Arm II: Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21. Patients in both arms undergo neuropsychological and clinical neurological assessment, blood collection for serum marker (e.g., serum glutamine and nerve growth factor) analysis, and quality of life assessment on days 1, 21, and 42. After completion of study treatment, patients are followed for an additional 21 days. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Interventions
DRUGGlutamine
Administered orally twice daily for 21 days
OTHERPlacebo
Administered orally twice daily for 21 days
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Patients between the age of 5 and 21 years old. * Patients who demonstrate the ability to complete the assessment instruments at baseline. * Patients who are diagnosed with leukemia or solid tumors and are expected to receive a cumulative dose of \> or = to 6mg/m2 of vincristine, or \> 6mg if individual vincristine doses are capped at 2mg according to primary cancer treatment protocol, over a 30-week period.
Exclusion criteria
* Patients with primary CNS tumors other than medulloblastoma or patients with CNS metastasis. * Patients with recurrent disease. * Patients with Grade II, III or IV neurological status by the NCI CTC (Ver. 3.0) on clinical exam. * Patients who have already received \> 8mg/m2 of vincristine, or \> 8mg if individual vincristine doses are capped at 2mg according to primary cancer treatment protocol, during their course of therapy at time of consent. * Patients with hepatic encephalopathy or hyperammonemia. * Patients with a focally abnormal neurologic exam.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Vincristine-induced Peripheral Neuropathy | Up to 30 weeks from baseline while on Vincristine treatment |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Progression of Neuropathy | 42 days |
Countries
United States
Participant flow
Recruitment details
All subjects were consented according to Institutional Review Board approved guidelines during out routine outpatient or inpatient stay. The period of recruitment was from January 2007 to July 2011.
Pre-assignment details
Fifty-six patients were enrolled and 49 were evaluable, with the reasons for removal from study after randomization due to: change in clinical status (N=3), family withdrew (N=2), family relocation (N=1) and other (N=1). 49 patients were randomized to the glutamine or placebo arm.
Participants by arm
| Arm | Count |
|---|---|
| Arm I: Glutamine Beginning 1 week after administration of vincristine chemotherapy, patients receive oral glutamine twice daily on days 1-21.
Glutamine: Administered orally twice daily for 21 days | 24 |
| Arm II: Placebo Beginning 1 week after administration of vincristine chemotherapy, patients receive oral placebo twice daily on days 1-21.
Placebo: Administered orally twice daily for 21 days | 25 |
| Total | 49 |
Baseline characteristics
| Characteristic | Arm I: Glutamine | Arm II: Placebo | Total |
|---|---|---|---|
| Age, Continuous | 11 years | 10 years | 11 years |
| Region of Enrollment United States | 24 participants | 25 participants | 49 participants |
| Sex: Female, Male Female | 14 Participants | 12 Participants | 26 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 25 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 |
Outcome results
Primary
Incidence of Vincristine-induced Peripheral Neuropathy
Time frame: Up to 30 weeks from baseline while on Vincristine treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Glutamine | Incidence of Vincristine-induced Peripheral Neuropathy | 24 participants |
| Arm II: Placebo | Incidence of Vincristine-induced Peripheral Neuropathy | 25 participants |
Secondary
Number of Participants With Progression of Neuropathy
Time frame: 42 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Glutamine | Number of Participants With Progression of Neuropathy | 11 participants |
| Arm II: Placebo | Number of Participants With Progression of Neuropathy | 19 participants |