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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01506453
Recruitment Status : Completed
First Posted : January 10, 2012
Last Update Posted : January 9, 2018
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Neuropathy Neuropathic Pain Drug: gabapentin Drug: placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Supportive Care
Official Title: Therapeutic Interventions For Peripheral Neuropathy/Neuropathic Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL) On Total XVI Protocol
Actual Study Start Date : January 24, 2012
Actual Primary Completion Date : January 2, 2018
Actual Study Completion Date : January 2, 2018

Arm Intervention/treatment
Active Comparator: Gabapentin
Active treatment arm.
Drug: gabapentin
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.
Other Name: Treatment Arm

Placebo Comparator: Placebo
Placebo arm.
Drug: placebo
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.
Other Name: Placebo Arm

Primary Outcome Measures :
  1. Daily total dose of oral morphine (mg/kg/day). [ Time Frame: Daily beginning day 1 for a maximum of 21 days. ]
    A quantity measured by pill count and/or adherence interview

Secondary Outcome Measures :
  1. Pain scores right now [ Time Frame: Daily beginning day 1 through a maximum of 21 days. ]
    A score ranging from 0 to 10, measured by age appropriate validated pain scale

  2. Pain score during the previous 24 hours [ Time Frame: Daily beginning day 1 through a maximum of 21 days ]
    A score ranging from 0 to 10, measured by age appropriate validated pain scale

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01506453

United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Principal Investigator: Doralina Anghelescu, MD St. Jude Children's Research Hospital

Additional Information:
Responsible Party: St. Jude Children's Research Hospital Identifier: NCT01506453     History of Changes
Other Study ID Numbers: TINALL
NCI-2012-00413 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: January 10, 2012    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:
Acute Lymphoblastic Leukemia
Neuropathic Pain
TOTAL XVI Protocol

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antiparkinson Agents