Trial Outcomes & Findings for Therapeutic Interventions For Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL) (NCT NCT01506453)

Last Updated: 2019-06-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

Daily beginning day 1 for a maximum of 21 days.

Results posted on

2019-06-19

Participant Flow

51 participants were enrolled and screened between January 2012 and October 2016.

The remaining 51 participants were randomized to take gabapentin or placebo.

Participant milestones

Participant milestones
Measure	Gabapentin Active treatment arm. 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.	Placebo Placebo arm. 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.
Overall Study STARTED	25	26
Overall Study COMPLETED	25	24
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Gabapentin Active treatment arm. 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.	Placebo Placebo arm. 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.
Overall Study Withdrawal prior to treatment	0	2

Baseline Characteristics

2 of 26 patients in the placebo group did not receive the placebo and therefore no data was generated based on them.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gabapentin n=25 Participants Active treatment arm 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.	Placebo n=26 Participants Placebo arm 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.	Total n=51 Participants Total of all reporting groups
Age, Continuous	7.88 years STANDARD_DEVIATION 5.69 • n=25 Participants	7.08 years STANDARD_DEVIATION 3.90 • n=26 Participants	7.48 years STANDARD_DEVIATION 4.83 • n=51 Participants
Sex: Female, Male Female	11 Participants n=25 Participants	10 Participants n=26 Participants	21 Participants n=51 Participants
Sex: Female, Male Male	14 Participants n=25 Participants	16 Participants n=26 Participants	30 Participants n=51 Participants
Race/Ethnicity, Customized Baseline Measures · Asian and White	0 Participants n=25 Participants	1 Participants n=26 Participants	1 Participants n=51 Participants
Race/Ethnicity, Customized Baseline Measures · Black	1 Participants n=25 Participants	2 Participants n=26 Participants	3 Participants n=51 Participants
Race/Ethnicity, Customized Baseline Measures · Black and White	1 Participants n=25 Participants	2 Participants n=26 Participants	3 Participants n=51 Participants
Race/Ethnicity, Customized Baseline Measures · White	23 Participants n=25 Participants	21 Participants n=26 Participants	44 Participants n=51 Participants
Region of Enrollment United States	25 Participants n=25 Participants	26 Participants n=26 Participants	51 Participants n=51 Participants
Daily "pain score right now"	3.12 units on a scale STANDARD_DEVIATION 1.86 • n=25 Participants • 2 of 26 patients in the placebo group did not receive the placebo and therefore no data was generated based on them.	3.58 units on a scale STANDARD_DEVIATION 1.42 • n=24 Participants • 2 of 26 patients in the placebo group did not receive the placebo and therefore no data was generated based on them.	3.35 units on a scale STANDARD_DEVIATION 1.65 • n=49 Participants • 2 of 26 patients in the placebo group did not receive the placebo and therefore no data was generated based on them.
baseline pain score last 24 hours	4.08 units on a scale STANDARD_DEVIATION 1.66 • n=25 Participants • 2 of 26 patients in the placebo group did not receive the placebo and therefore no data was generated based on them.	4.31 units on a scale STANDARD_DEVIATION 1.76 • n=24 Participants • 2 of 26 patients in the placebo group did not receive the placebo and therefore no data was generated based on them.	4.20 units on a scale STANDARD_DEVIATION 1.70 • n=49 Participants • 2 of 26 patients in the placebo group did not receive the placebo and therefore no data was generated based on them.

PRIMARY outcome

Timeframe: Daily beginning day 1 for a maximum of 21 days.

Population: The daily morphine dosage will be modeled as longitudinal observations with treatment (gabapentin vs. placebo) group, and if necessary, other clinical factors such as age category for pain assessment (0-3yr, 4-7yr, \>7yr), baseline pain score, and ALL risk classification, as explanatory factors, using repeated measure linear models

Outcome measures

Outcome measures
Measure	Gabapentin n=25 Participants Active treatment arm. 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.	Placebo n=24 Participants Placebo arm. 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.
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 1	0.38267 mg/kg/day Standard Deviation 0.28921	0.27433 mg/kg/day Standard Deviation 0.19299
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 2	0.43685 mg/kg/day Standard Deviation 0.33788	0.31816 mg/kg/day Standard Deviation 0.16012
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 3	0.37281 mg/kg/day Standard Deviation 0.32935	0.27961 mg/kg/day Standard Deviation 0.18509
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 4	0.40384 mg/kg/day Standard Deviation 0.32469	0.35343 mg/kg/day Standard Deviation 0.18688
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 5	0.37662 mg/kg/day Standard Deviation 0.31263	0.37920 mg/kg/day Standard Deviation 0.22471
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 6	0.45679 mg/kg/day Standard Deviation 0.45450	0.43972 mg/kg/day Standard Deviation 0.19838
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 7	0.50961 mg/kg/day Standard Deviation 0.43643	0.37181 mg/kg/day Standard Deviation 0.22883
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 8	0.50767 mg/kg/day Standard Deviation 0.53570	0.38188 mg/kg/day Standard Deviation 0.28251
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 9	0.49234 mg/kg/day Standard Deviation 0.33366	0.34524 mg/kg/day Standard Deviation 0.20164
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 10	0.44392 mg/kg/day Standard Deviation 0.37244	0.34660 mg/kg/day Standard Deviation 0.15843
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 11	0.50981 mg/kg/day Standard Deviation 0.67516	0.29937 mg/kg/day Standard Deviation 0.14111
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 12	0.57798 mg/kg/day Standard Deviation 0.51346	0.40090 mg/kg/day Standard Deviation 0.21956
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 13	0.68183 mg/kg/day Standard Deviation 0.51698	0.45933 mg/kg/day Standard Deviation 0.32854
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 14	0.53028 mg/kg/day Standard Deviation 0.57870	0.34957 mg/kg/day Standard Deviation 0.15460
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 15	0.55939 mg/kg/day Standard Deviation 0.69755	0.36731 mg/kg/day Standard Deviation 0.23170
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 16	0.37643 mg/kg/day Standard Deviation 0.37817	0.48481 mg/kg/day Standard Deviation 0.37075
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 17	0.38837 mg/kg/day Standard Deviation 0.30190	0.54960 mg/kg/day Standard Deviation 0.47579
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 18	0.65013 mg/kg/day Standard Deviation 0.96603	0.13605 mg/kg/day Standard Deviation NA Measure of dispersion not calculated.
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 19	0.84586 mg/kg/day Standard Deviation 1.08656	0.14123 mg/kg/day Standard Deviation 0.00740
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 20	1.12358 mg/kg/day Standard Deviation 1.37790	0.15108 mg/kg/day Standard Deviation NA Measure of dispersion not calculated.
Daily Total Dose of Oral Morphine (mg/kg/Day). Day 21	0.14981 mg/kg/day Standard Deviation NA Measure of dispersion not calculated.	—

SECONDARY outcome

Timeframe: Daily beginning day 1 through a maximum of 21 days.

Population: There were participants in the Gabapentin and Placebo groups that did not have pain assessments at various time points. Pain score was 0 for each placebo participant on days 19, 20 and 21.

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.

Outcome measures

SECONDARY outcome

Timeframe: Daily beginning day 1 through a maximum of 21 days

Population: There were participants in the Gabapentin and Placebo groups that did not have pain assessments at various time points. Pain score was 0 for each placebo participant on days 20 and 21.

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.

Outcome measures

Adverse Events

Gabapentin

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Gabapentin n=25 participants at risk Active treatment arm. 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.	Placebo n=24 participants at risk Placebo arm. 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.
Nervous system disorders Depressed level of consciousness	20.0% 5/25 • Number of events 5 • through study completion, up to 21 days Adverse events will be submitted by a member of the study team to the IRB using the existing institutional online reporting mechanisms. All study-related AEs will be collected in the database, regardless of their grade.	20.8% 5/24 • Number of events 6 • through study completion, up to 21 days Adverse events will be submitted by a member of the study team to the IRB using the existing institutional online reporting mechanisms. All study-related AEs will be collected in the database, regardless of their grade.
Psychiatric disorders Anxiety	4.0% 1/25 • Number of events 1 • through study completion, up to 21 days Adverse events will be submitted by a member of the study team to the IRB using the existing institutional online reporting mechanisms. All study-related AEs will be collected in the database, regardless of their grade.	0.00% 0/24 • through study completion, up to 21 days Adverse events will be submitted by a member of the study team to the IRB using the existing institutional online reporting mechanisms. All study-related AEs will be collected in the database, regardless of their grade.

Additional Information

Doralina Anghelescu, MD

St. Jude Children's Research Hospital

Phone: (901) 595-4034

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Gabapentin n=25 Participants Active treatment arm. 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.	Placebo n=24 Participants Placebo arm. 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.
Pain Scores Right Now Day 1	1.64000 score on a scale 0-10 Standard Deviation 1.89033	1.69565 score on a scale 0-10 Standard Deviation 2.09837
Pain Scores Right Now Day 2	2.00000 score on a scale 0-10 Standard Deviation 2.19848	1.16667 score on a scale 0-10 Standard Deviation 1.57885
Pain Scores Right Now Day 3	1.88000 score on a scale 0-10 Standard Deviation 2.60320	0.75000 score on a scale 0-10 Standard Deviation 1.25974
Pain Scores Right Now Day 4	1.92000 score on a scale 0-10 Standard Deviation 2.64449	0.83333 score on a scale 0-10 Standard Deviation 1.30773
Pain Scores Right Now Day 5	1.64000 score on a scale 0-10 Standard Deviation 1.97653	1.00000 score on a scale 0-10 Standard Deviation 1.44463
Pain Scores Right Now Day 6	1.40000 score on a scale 0-10 Standard Deviation 1.75594	0.79167 score on a scale 0-10 Standard Deviation 1.38247
Pain Scores Right Now Day 7	2.20000 score on a scale 0-10 Standard Deviation 2.17945	0.91667 score on a scale 0-10 Standard Deviation 1.50121
Pain Scores Right Now Day 8	1.32000 score on a scale 0-10 Standard Deviation 1.90875	0.56522 score on a scale 0-10 Standard Deviation 1.23679
Pain Scores Right Now Day 9	1.48000 score on a scale 0-10 Standard Deviation 2.06398	0.86957 score on a scale 0-10 Standard Deviation 1.63219
Pain Scores Right Now Day 10	1.16000 score on a scale 0-10 Standard Deviation 1.65025	0.39130 score on a scale 0-10 Standard Deviation 0.83878
Pain Scores Right Now Day 11	1.16000 score on a scale 0-10 Standard Deviation 1.90788	0.82609 score on a scale 0-10 Standard Deviation 1.26678
Pain Scores Right Now Day 12	1.21739 score on a scale 0-10 Standard Deviation 1.88189	1.00000 score on a scale 0-10 Standard Deviation 1.50756
Pain Scores Right Now Day 13	1.04348 score on a scale 0-10 Standard Deviation 1.46095	0.69565 score on a scale 0-10 Standard Deviation 1.39593
Pain Scores Right Now Day 14	0.82609 score on a scale 0-10 Standard Deviation 1.11405	0.52174 score on a scale 0-10 Standard Deviation 1.23838
Pain Scores Right Now Day 15	0.90909 score on a scale 0-10 Standard Deviation 1.63034	0.60870 score on a scale 0-10 Standard Deviation 1.23359
Pain Scores Right Now Day 16	1.29412 score on a scale 0-10 Standard Deviation 1.99263	0.31250 score on a scale 0-10 Standard Deviation 0.87321
Pain Scores Right Now Day 17	0.40000 score on a scale 0-10 Standard Deviation 0.91026	0.21429 score on a scale 0-10 Standard Deviation 0.80178
Pain Scores Right Now Day 18	1.45455 score on a scale 0-10 Standard Deviation 2.54416	0.25000 score on a scale 0-10 Standard Deviation 0.86603
Pain Scores Right Now Day 19	1.00000 score on a scale 0-10 Standard Deviation 1.41421	0 score on a scale 0-10 Standard Deviation 0
Pain Scores Right Now Day 20	1.33333 score on a scale 0-10 Standard Deviation 1.15470	0 score on a scale 0-10 Standard Deviation 0
Pain Scores Right Now Day 21	—	0 score on a scale 0-10 Standard Deviation 0

Measure	Gabapentin n=25 Participants Active treatment arm. 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.	Placebo n=24 Participants Placebo arm. 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.
Pain Score During the Previous 24 Hours Day 1	3.48000 score on a scale 0-10 Standard Deviation 2.50200	3.41667 score on a scale 0-10 Standard Deviation 2.39414
Pain Score During the Previous 24 Hours Day 2	3.16000 score on a scale 0-10 Standard Deviation 2.37487	2.20833 score on a scale 0-10 Standard Deviation 2.14637
Pain Score During the Previous 24 Hours Day 3	3.08000 score on a scale 0-10 Standard Deviation 2.28983	1.87500 score on a scale 0-10 Standard Deviation 1.87228
Pain Score During the Previous 24 Hours Day 4	2.80000 score on a scale 0-10 Standard Deviation 2.43242	2.12500 score on a scale 0-10 Standard Deviation 2.64267
Pain Score During the Previous 24 Hours Day 5	2.80000 score on a scale 0-10 Standard Deviation 2.61406	2.00000 score on a scale 0-10 Standard Deviation 2.14679
Pain Score During the Previous 24 Hours Day 6	2.28000 score on a scale 0-10 Standard Deviation 1.92614	1.91667 score on a scale 0-10 Standard Deviation 2.20507
Pain Score During the Previous 24 Hours Day 7	2.96000 score on a scale 0-10 Standard Deviation 2.22636	1.16667 score on a scale 0-10 Standard Deviation 1.60615
Pain Score During the Previous 24 Hours Day 8	2.76000 score on a scale 0-10 Standard Deviation 2.24128	1.69565 score on a scale 0-10 Standard Deviation 1.91726
Pain Score During the Previous 24 Hours Day 9	2.16000 score on a scale 0-10 Standard Deviation 2.21133	1.34783 score on a scale 0-10 Standard Deviation 1.74795
Pain Score During the Previous 24 Hours Day 10	2.16000 score on a scale 0-10 Standard Deviation 2.24870	1.43478 score on a scale 0-10 Standard Deviation 1.64665
Pain Score During the Previous 24 Hours Day 11	2.32000 score on a scale 0-10 Standard Deviation 2.05589	1.56522 score on a scale 0-10 Standard Deviation 1.67403
Pain Score During the Previous 24 Hours Day 12	2.41667 score on a scale 0-10 Standard Deviation 2.43018	1.52174 score on a scale 0-10 Standard Deviation 1.90381
Pain Score During the Previous 24 Hours Day 13	2.50000 score on a scale 0-10 Standard Deviation 2.20671	1.60870 score on a scale 0-10 Standard Deviation 1.85225
Pain Score During the Previous 24 Hours Day 14	2.60870 score on a scale 0-10 Standard Deviation 2.27115	1.56522 score on a scale 0-10 Standard Deviation 1.64665
Pain Score During the Previous 24 Hours Day 15	2.54545 score on a scale 0-10 Standard Deviation 2.15423	1.39130 score on a scale 0-10 Standard Deviation 1.67167
Pain Score During the Previous 24 Hours Day 16	2.23529 score on a scale 0-10 Standard Deviation 1.82104	1.56250 score on a scale 0-10 Standard Deviation 1.82460
Pain Score During the Previous 24 Hours Day 17	1.40000 score on a scale 0-10 Standard Deviation 1.59463	1.92857 score on a scale 0-10 Standard Deviation 2.01778
Pain Score During the Previous 24 Hours Day 18	2.36364 score on a scale 0-10 Standard Deviation 3.00908	1.00000 score on a scale 0-10 Standard Deviation 1.65145
Pain Score During the Previous 24 Hours Day 19	1.40000 score on a scale 0-10 Standard Deviation 1.34164	0.40000 score on a scale 0-10 Standard Deviation 0.89443
Pain Score During the Previous 24 Hours Day 20	2.33333 score on a scale 0-10 Standard Deviation 0.57735	0 score on a scale 0-10 Standard Deviation 0
Pain Score During the Previous 24 Hours Day 21	—	0 score on a scale 0-10 Standard Deviation 0