Therapeutic Interventions For Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL)

Study Overview
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Brief Summary
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Neuropathic pain / peripheral neuropathy (NP/PN) is a known painful complication of vincristine (VCR) therapy; evidence supporting the best treatment plan for pediatric patients is limited. Gabapentin is frequently used for VCR-related NP/PN, with variable dosing and scheduling regimens, and with varying measures of success. The hypothesis of the study is that gabapentin will reduce the severity of NP/PN in patients receiving vincristine during treatment for ALL on the Total XVI protocol (or for those being treated as per TOTXVI protocol), as measured by two outcome measures: the daily dose of morphine used as needed for pain in addition to either gabapentin or placebo, as randomized, and the pain scores assessed daily.

Detailed Description
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Patients with ALL on Total XVI ((or for those being treated as per TOTXVI protocol) who experience NP/PN after specific doses of vincristine are eligible to enroll in the study as soon as the diagnosis of NP/PN related to VCR is established. The qualifying doses of vincristine have been selected because they fall in the schedule of weekly vincristine doses as per Total XVI, and 2 additional weekly vincristine doses are anticipated according to the protocol. Participants will be randomized to receive gabapentin or placebo upon enrollment. Morphine will be available to both groups as needed for pain at any time on the study. At the time of enrollment, and daily thereafter until completion of the study drug, data will be collected for pain assessment, and the daily dose of oral morphine used will be collected. Data regarding the pain type, quality, and location, as well as treatments used to manage pain will be assessed on a daily basis for the diagnostic event and for the period following the next two administrations of VCR treated with the study drug. Primary Objective: To assess the analgesic efficacy of gabapentin in controlling VCR-related NP/PN in participants with ALL, by comparing the morphine daily dose (mg/kg/day) used to control NP/PN as a primary or a rescue regimen in the gabapentin vs. placebo groups. Secondary Objective: To compare the pain scores in the gabapentin and placebo groups as recorded by pain score right now and pain score average for previous 24 hours.

Official Title
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Therapeutic Interventions For Peripheral Neuropathy/Neuropathic Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL) On Total XVI Protocol

Conditions
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Acute Lymphoblastic Leukemia, Neuropathy, Neuropathic Pain

Intervention / Treatment
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* Drug: gabapentin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is enrolled on Total XVI or who are being treated as per TOTXVI protocol Participant is 1 year of age or older Participant has symptoms of NP/PN with onset no more than 7 days after one of the following vincristine doses ± 3 days: protocol week 1, week 2 (induction), week 7 (reinduction I), or week 17 (reinduction II). Patient is expected to receive 2 doses of vincristine in weekly intervals as outlined by the Total XVI protocol (or for those being treated as per TOTXVI protocol) while on study drug (i.e. no known dosage reductions or planned missed doses). Participant is able and willing to take oral medications. Exclusion Criteria: Previous participation in this study Participant is receiving gabapentin for another indication at the time of diagnosis of NP/PN or has received gabapentin previously. Pregnancy. Female participants of childbearing potential must have documented negative urine or serum pregnancy test result not older than 7 days. Male patients with reproductive potential will be counseled not to procreate during the study. Impaired renal function: decreased eGFR (<60ml/min/1.73m^2 as estimated by the revised Schwartz equation) Participant has allergy or other contraindication for either morphine or gabapentin therapy. Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gabapentin<br>Active treatment arm. | Drug: gabapentin<br>* Participants randomized to the active treatment arm will receive gabapentin 20mg/kg/day PO divided into 3 doses and rounded to the nearest 100 mg for capsules and 10 mg for liquid preparation.<br>* Other names: Treatment Arm;|
| Placebo Comparator: Placebo<br>Placebo arm. | Drug: placebo<br>* Participants randomized to the placebo treatment arm will receive look-alike capsules or liquid in a respective capsule size or liquid measure equivalent to the active treatment arm, but which contain no active treatment.<br>* Other names: Placebo Arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Total Dose of Oral Morphine (mg/kg/Day). | The response to therapy will be measured by pain intensity scores and daily use of morphine doses for breakthrough pain as described in the study objectives. Daily assessments will continue during treatment with the study drug (gabapentin or placebo) irrespective of patient response to study treatment. and toddlers (less than age 4 years) or other children who cannot self report, use the FLACC Scale Score each component as a subscore (face, legs, activity, cry, consolability) Total subscores to determine FLACC score Older children (ages 4 to 7 years) who can self-report, use the Faces Pain Scale-Revised (FPS-R) Ages >7 years, Self report using a numeric scale 0-10 without reference to Faces Pain Scale-Revised (FPS-R) Pain score 0 means no pain and 10 means worst pain. The scale information for the FLACC and FPS-R scales are similar. | Daily beginning day 1 for a maximum of 21 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Scores Right Now | A score ranging from 0 to 10, measured by age appropriate validated pain scale. Because there was only one patient during day 21 time point for this treatment group, the mean and standard deviation could not be calculated. Infants and toddlers (less than age 4 years) or other children who cannot self report, use the FLACC Scale Score each component as a subscore (face, legs, activity, cry, consolability) Total subscores to determine FLACC score Older children (ages 4 to 7 years) who can self-report, use the Faces Pain Scale-Revised (FPS-R) Ages >7 years, Self report using a numeric scale 0-10 without reference to Faces Pain Scale-Revised (FPS-R) Pain score 0 means no pain and 10 means worst pain.The scale information for the FLACC and FPS-R scales are similar. | Daily beginning day 1 through a maximum of 21 days. | 
| Pain Score During the Previous 24 Hours | A score ranging from 0 to 10, measured by age appropriate validated pain scale. Because there was only one patient during day 21 time point for this treatment group, the mean and standard deviation could not be calculated.Infants and toddlers (less than age 4 years) or other children who cannot self report, use the FLACC Scale Score each component as a subscore (face, legs, activity, cry, consolability) Total subscores to determine FLACC score Older children (ages 4 to 7 years) who can self-report, use the Faces Pain Scale-Revised (FPS-R) Ages >7 years, Self report using a numeric scale 0-10 without reference to Faces Pain Scale-Revised (FPS-R) Pain score 0 means no pain and 10 means worst pain.The scale information for the FLACC and FPS-R scales are similar. | Daily beginning day 1 through a maximum of 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lymphoblastic Leukemia, Neuropathy, Neuropathic Pain, Vincristine, TOTAL XVI Protocol