Trial Outcomes & Findings for Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer (NCT NCT00369564)

Last Updated: 2021-08-11

Results Overview

A neurological exam will be completed at baseline and at study week 5 for both strata. An additional exam at week 10 will be done for patients in Stratum 1. Additional exams will be done at any time if the treating oncologist deems it clinically necessary . Neurotoxicity will be scored using a standardized neurological exam form developed for the study that is based on the Modified "Balis" Pediatric Scale of Peripheral Neuropathies. Treatment groups will be compared with respect to the proportion experiencing a grade 2 or higher toxicity from the following list of neurologic toxicities captured on the Neurologic Exam Form including sensory neuropathy, motor neuropathy, laryngeal nerve, constipation/neuro-constipation, jaw pain, or other specified abnormalities noted by the attending physician. Percentage of patients with one or more Grade 2 or higher noted neurotoxicity symptoms on any item in the Balis scale will compared between arms.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

250 participants

Primary outcome timeframe

10 weeks

Results posted on

2021-08-11

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I Glutamic Acid Patients receive oral l-glutamic acid hydrocloride 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1). Patients with a body surface area (BSA) less than 1.0 m\^2 will receive a total of 750 mg/day of oral glutamic acid . Patients with a body surface area (BSA) greater or equal to1.0 m\^2 will receive a total of 1500 mg/day of oral glutamic acid .	Arm II Placebo Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1). Placebo capsules are identical in appearance to the active oral glutamic acid capsules but instead each capsule contains 324 mg of microcrystalline cellulose as a filler, 3 mg of magnesium stearate as a lubricant and 3 mg silicone dioxide as a drying agent for a total fill weight of 330 mg. The manufacturer has certified that the placebo contains no active agent. Patients with a body surface area (BSA) less than 1.0 m\^2 will receive a 1 capsule of placebo 3 times daily (total 3 capsules daily). Patients with a body surface area (BSA) greater or equal to1.0 m\^2 will receive a 2 placebo capsules 3 times daily (total 6 capsules daily). .
Overall Study STARTED	127	123
Overall Study COMPLETED	84	100
Overall Study NOT COMPLETED	43	23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I Glutamic Acid n=127 Participants Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Arm II Placebo n=123 Participants Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Total n=250 Participants Total of all reporting groups
Age, Categorical <=18 years	123 Participants n=5 Participants	117 Participants n=7 Participants	240 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	8.5 years STANDARD_DEVIATION 4.8 • n=5 Participants	8.6 years STANDARD_DEVIATION 4.9 • n=7 Participants	8.6 years STANDARD_DEVIATION 4.9 • n=5 Participants
Sex/Gender, Customized Gender- Female	46 participants n=5 Participants	53 participants n=7 Participants	99 participants n=5 Participants
Sex/Gender, Customized Gender- Male	81 participants n=5 Participants	69 participants n=7 Participants	150 participants n=5 Participants
Sex/Gender, Customized Gender Not Reported	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	127 participants n=5 Participants	123 participants n=7 Participants	250 participants n=5 Participants

PRIMARY outcome

Timeframe: 10 weeks

Population: Patients reporting baseline and post-baseline observation

Outcome measures

Outcome measures
Measure	Arm I Glutamic Acid n=97 Participants Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Arm II Placebo n=107 Participants Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Neurotoxicity as Measured by a Scored Neurologic Examination at Baseline, 5 Weeks, and 10 Weeks (if Applicable)	26 percentage of participants 95% Confidence Interval 4.4 • Interval 18.0 to 37.0	34 percentage of participants 95% Confidence Interval 4.5 • Interval 23.0 to 41.0

SECONDARY outcome

Timeframe: 10 weeks

Population: Stratum 2 with a \>= grade 2 neurotoxicity

Number of participants with neurotoxicity observed treated with l-glutamic acid hydrochloride as compared to the number of participants with neurotoxicity observed in the placebo control group

Outcome measures

Outcome measures
Measure	Arm I Glutamic Acid n=79 Participants Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Arm II Placebo n=88 Participants Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Number of Participants With Neurotoxicity Observed	21 Participants	25 Participants

SECONDARY outcome

Timeframe: 10 weeks

Population: Number in stratum 1 and stratum 2 that completed

We will determine if a greater proportion of patients receiving l-glutamic acid hydrochloride are able to receive 100% of their scheduled doses of vincristine as compared to those in the placebo control group

Outcome measures

Outcome measures
Measure	Arm I Glutamic Acid n=127 Participants Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Arm II Placebo n=123 Participants Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Ability to Receive All Scheduled Doses of Vincristine	84 Participants	100 Participants

SECONDARY outcome

Timeframe: 10 Weeks

Population: Participants who returned a post baseline Neurotox Questionnaire

Types of neurotoxicities reported. Each patient was only counted once for each type of neurotoxicity, but a patient could be counted in more than 1 type of neurotoxicity. For example, if a patient experienced constipation 3 times, they are included once for constipation. If a patient experienced sensory changes and motor changes, they are included once for sensory changes and once for motor changes.

Outcome measures

Outcome measures
Measure	Arm I Glutamic Acid n=127 Participants Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Arm II Placebo n=123 Participants Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Types of Neurotoxicities Constipation	11 Participants	14 Participants
Types of Neurotoxicities Sensory Changes	11 Participants	13 Participants
Types of Neurotoxicities Motor Changes	10 Participants	13 Participants
Types of Neurotoxicities Jaw Pain	4 Participants	2 Participants
Types of Neurotoxicities Laryngeal Nerve Dysfunction	2 Participants	1 Participants

Adverse Events

Arm I Glutamic Acid

Serious events: 9 serious events

Other events: 16 other events

Deaths: 0 deaths

Arm II Placebo

Serious events: 6 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm I Glutamic Acid n=127 participants at risk Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Arm II Placebo n=123 participants at risk Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Gastrointestinal disorders Vomiting	7.1% 9/127 • Number of events 10 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	2.4% 3/123 • Number of events 3 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
General disorders Pain	5.5% 7/127 • Number of events 7 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	2.4% 3/123 • Number of events 6 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.

Additional Information

Scott Bradfield, MD

Nemours Children's Clinic

Phone: 904-697-3793

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I Glutamic Acid n=127 participants at risk Patients receive oral glutamic acid 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).	Arm II Placebo n=123 participants at risk Patients receive oral placebo 3 times daily beginning prior to the first dose of vincristine and continuing through week 5 (stratum 2) or week 10 (stratum 1).
Cardiac disorders Hypertension	0.00% 0/127 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Endocrine disorders Adrenal Insufficiency	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
General disorders Pain	0.00% 0/127 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
General disorders Tumor lysis syndrome	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Hepatobiliary disorders Pancreatitis	0.00% 0/127 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Infections and infestations Febrile neutropenia	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 2 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Infections and infestations Infection-Other	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Infections and infestations Infection with unknown ANC	0.79% 1/127 • Number of events 2 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Nervous system disorders Cognitive disturbance	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Nervous system disorders Confusion	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Nervous system disorders Encephalopathy	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Nervous system disorders Leukoencephalopathy (radiographic findings)	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Nervous system disorders Seizure	2.4% 3/127 • Number of events 3 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	2.4% 3/123 • Number of events 3 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Nervous system disorders Somnolence	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Nervous system disorders Syncope (fainting)	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other	0.79% 1/127 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.00% 0/123 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.
Vascular disorders Vascular - Other	0.00% 0/127 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.	0.81% 1/123 • Number of events 1 • 10 weeks Subjects and parents completed daily study medication logs and noted any adverse events or symptoms. Site personnel reviewed study medication logs with subjects to assess for adverse events and completed an in-person neurological exam and chemistry profile at weeks 5 and 10 to assess for adverse events. Adverse events reviewed by independent DSMB.