Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
Conditions
Keywords
Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Erwinaze, asparaginase, Eusa Pharma, Pharmacokinetic study, NSAA
Brief summary
This study will utilize Erwinaze via intravenous administration in patients between the ages of 1 and 30 who have experienced an allergy to their frontline therapy. The study will determine the proportion of patients with 2 day nadir serum asparaginase activity levels that are \>0.1 IU/mL during the first 2 weeks of treatment with 3 times per week IV dosing.
Interventions
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma, * Ages \>/= 1 and \</= to 30 years at the time of initial diagnosis * Undergoing asparaginase treatment for ALL or lymphoblastic lymphoma * Documented Grade 2 or higher hypersensitivity reaction to native or pegylated E. coli asparaginase or Calaspargase pegol * Must have two remaining weeks of native E. coli asparaginase treatment or 1 remaining dose of either Pegaspargase or Calaspargase pegol * Direct bilirubin less than or equal to Grade 2 * Amylase and lipase within normal limits (per institutional standards) * Signed informed consent by the patient is greater than or equal to 18 years or by the parent if the patient is younger than 18 years old.
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two Day Nadir Serum Asparaginase Activity (NSAA) Level | 48 hours post-dose 5 | To report the mean 2 day NSAA levels (48 hour levels taken after the 5th dose) that are \> or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 48 Hours | 48 hours post-dose 5 | To report the proportion of participants achieving 2 day NSAA levels (48 hour levels taken after the 5th dose) that are \> or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose. |
| Three Day NSAA Level | 72 hours post-dose 6 | To report the mean 3 day NSAA levels (72 hour levels taken after the 6th dose) that are \> or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose. |
| Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 72 Hours | 72 hours post-dose 6 | To report the proportion of participants achieving 3 day NSAA levels (72 hour levels taken after the 6th dose) that are \> or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose. |
| Nadir Serum Asparaginase Activity Over Time | 4 weeks to 30 weeks | To describe the NSAA over time in participants with ALL/Lymphoblastic Lymphoma who have/had developed hypersensitivity to native E. coli asparaginase, Pegaspargase or Calaspargase pegol and are receiving intravenous Erwinaze 3 times per week for a prolonged duration (4-30 weeks). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Population All patients who received at least one dose of Erwinaze | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Other | 2 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 7.9 years STANDARD_DEVIATION 5.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 23 / 30 |
| serious Total, serious adverse events | 15 / 30 |
Outcome results
Primary
Two Day Nadir Serum Asparaginase Activity (NSAA) Level
To report the mean 2 day NSAA levels (48 hour levels taken after the 5th dose) that are \> or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time frame: 48 hours post-dose 5
Population: The Pharmacokinetic (PK) population consisted of all participants who received at least 1 dose of Erwinaze and were considered evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Erwinaze | Two Day Nadir Serum Asparaginase Activity (NSAA) Level | 0.32 (IU/mL) | Standard Deviation 0.23 |
Secondary
Nadir Serum Asparaginase Activity Over Time
To describe the NSAA over time in participants with ALL/Lymphoblastic Lymphoma who have/had developed hypersensitivity to native E. coli asparaginase, Pegaspargase or Calaspargase pegol and are receiving intravenous Erwinaze 3 times per week for a prolonged duration (4-30 weeks).
Time frame: 4 weeks to 30 weeks
Population: This population consisted of participants who completed Course 4 with Pharmacokinetic(s) (PK) assessments 48 hours after dose 5 (week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Erwinaze | Nadir Serum Asparaginase Activity Over Time | 0.51 IU/mL | Standard Deviation 0.252 |
Secondary
Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 48 Hours
To report the proportion of participants achieving 2 day NSAA levels (48 hour levels taken after the 5th dose) that are \> or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time frame: 48 hours post-dose 5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-Label Erwinaze | Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 48 Hours | 20 Participants |
Secondary
Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 72 Hours
To report the proportion of participants achieving 3 day NSAA levels (72 hour levels taken after the 6th dose) that are \> or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time frame: 72 hours post-dose 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-Label Erwinaze | Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 72 Hours | 9 Participants |
Secondary
Three Day NSAA Level
To report the mean 3 day NSAA levels (72 hour levels taken after the 6th dose) that are \> or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.
Time frame: 72 hours post-dose 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Erwinaze | Three Day NSAA Level | 0.09 (IU/mL) | Standard Deviation 0.07 |