Leukemia, Lymphoma, Osteosarcoma
Conditions
Keywords
high dose methotrexate, Voraxaze, leucovorin, delayed elimination, methotrexate toxicity, rescue, renal insufficiency
Brief summary
The purpose of this study is to investigate whether the administration of Voraxaze reduces exposure to leucovorin and its active metabolite to below the level achieved in patients who have not received Voraxaze.
Interventions
DRUGglucarpidase, high-dose methotrexate, leucovorin
single intravenous dose
DRUGhigh-dose methotrexate, leucovorin
standard of care, leucovorin every 6 hours
Sponsors
BTG International Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Receiving High-dose methotrexate (HDMTX) with or without risk of methotrexate (MTX) toxicity, impaired renal function, and delayed MTX elimination * Require intravenous leucovorin
Exclusion criteria
* Arm A only: allergic reactions to lactose * Arm A only: hereditary fructose or galactose intolerance * Arm B only: delayed elimination of MTX
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Leucovorin | 5 minutes, 30 minutes, 1 hour, 2 hours and 3 hours post-LV administration | Geometric mean (6S)-leucovorin area under the plasma concentration vs. time curve from time 0 to the 3-hour time point. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A (High-dose Methotrexate, Leucovorin, and Glucarpidase) High-dose methotrexate, leucovorin, and glucarpidase
glucarpidase, high-dose methotrexate, leucovorin: single intravenous dose | 11 |
| B (High-dose Methotrexate and Leucovorin Without Glucarpidase) High-dose methotrexate and leucovorin without glucarpidase
high-dose methotrexate, leucovorin: standard of care, leucovorin every 6 hours | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | A (High-dose Methotrexate, Leucovorin, and Glucarpidase) | B (High-dose Methotrexate and Leucovorin Without Glucarpidase) | Total |
|---|---|---|---|
| Age, Continuous | 26.4 years STANDARD_DEVIATION 22.07 | 12.6 years STANDARD_DEVIATION 7.84 | 20.2 years STANDARD_DEVIATION 18.22 |
| Pre-glucarpidase (Arm A) or Pre-LV (Arm B) methotrexate plasma conc (umol/L) | 34.58 micromol/L STANDARD_DEVIATION 48.59 | 6.49 micromol/L STANDARD_DEVIATION 11 | 21.94 micromol/L STANDARD_DEVIATION 21.94 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 11 | 0 / 9 |
| serious Total, serious adverse events | 3 / 11 | 0 / 9 |
Outcome results
Primary
Pharmacokinetics (PK) of Leucovorin
Geometric mean (6S)-leucovorin area under the plasma concentration vs. time curve from time 0 to the 3-hour time point.
Time frame: 5 minutes, 30 minutes, 1 hour, 2 hours and 3 hours post-LV administration
Population: 3 participants were excluded from the PK population (all from Arm A), hence why the total participants is 17, not 20.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| A (High-dose Methotrexate, Leucovorin, and Glucarpidase) | Pharmacokinetics (PK) of Leucovorin | 6.43 micromol x hour/L |
| B (High-dose Methotrexate and Leucovorin Without Glucarpidase) | Pharmacokinetics (PK) of Leucovorin | 1.13 micromol x hour/L |