Clinical trial NCT01506453: Therapeutic Interventions For Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL)
Official title: Therapeutic Interventions For Peripheral Neuropathy/Neuropathic Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL) On Total XVI Protocol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Neuropathy
Neuropathic Pain
Keywords: Acute Lymphoblastic Leukemia
Neuropathy
Neuropathic Pain
Vincristine
TOTAL XVI Protocol
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2012-01-10
Enrollment: 51
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Daily Total Dose of Oral Morphine (mg/kg/Day).
timeFrame: Daily beginning day 1 for a maximum of 21 days.
Secondary outcomes:
measure: Pain Scores Right Now
timeFrame: Daily beginning day 1 through a maximum of 21 days.
measure: Pain Score During the Previous 24 Hours
timeFrame: Daily beginning day 1 through a maximum of 21 days
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Doralina Anghelescu, MD
role: PRINCIPAL_INVESTIGATOR
References: