Acute Lymphoblastic Leukemia
Conditions
Keywords
ALL, acute lymphoblastic leukemia, chemotherapy, asparaginase
Brief summary
The purpose of this study is to determine the safety and optimal dosing of L-asparaginase in adult patients with acute lymphoblastic leukemia (ALL) between the ages of 18 and 50 years.
Detailed description
This study has four treatment phases: 1) induction, 2) central nervous system therapy, 3) intensification, and 4) continuation. The induction phase lasts one month and eight drugs are used during this phase of treatment. The drugs are administered as follows: * Prednisone; on days 1-28: * Vincristine; on days 1, 8, 15, and 22: * Doxorubicin; on days 1 and 2: * Methotrexate; on day 3; * Leucovorin; 36 hours after methotrexate: * Asparaginase; on day 5: * Intra-thecal Cytarabine; on days 1, 15, and 29: * Intra-thecal Methotrexate/Hydrocortisone; on days 15 and 29 A bone marrow aspirate and biopsy will be obtained on day 15 and day 29 of induction therapy. If on day 29, the patients' bone marrow and peripheral blood counts are not in complete remission, then the patient may receive vincristine on days 29, 36 and 43. Bone marrow biopsy will be repeated weekly until complete remission is documented. If the patient does not achieve complete remission by day 49, they will be removed from the study. Central nervous system (CNS) therapy begins immediately after the end of the induction therapy. This phase of treatment should last 3 weeks. Treatment includes a series of spinal taps with the instillation of anti-leukemia drugs. Four spinal taps will be performed over a two week period. Anti-leukemia drugs will also be given orally. The drugs given are as follows: Vincristine; on day 1: Doxorubicin; on day 1: 6-mercaptopurine (6-MP); on days 1-14: Intra-thecal Methotrexate/Cytarabine; 4 times over 2 weeks. Radiation therapy (RT) will be delivered in 10 daily treatments during the CNS phase of therapy. The intensification phase begins as soon as the CNS phase ends and lasts approximately 30 weeks. It consists of cycles of chemotherapy repeated every 3 weeks, along with asparaginase administered weekly. The drugs given are as follows: Vincristine; day 1: Dexamethasone; days 1-5: 6-MP; days 1-14: Doxorubicin; day 1: Asparaginase; weekly: Methotrexate; weekly: Intra-thecal Hydrocortisone/Methotrexate/cytarabine; every 18 weeks. The continuation phase of treatment begins after the intensification phase. It consists of cycles of chemotherapy repeated every three weeks and will last until the patient is in remission for two years. The drugs given are: Vincristine; day 1 : Prednisone or Dexamethasone; days 1-5: 6-MP; days 1-14: Methotrexate; weekly: Intra-thecal Methotrexate/Cytarabine/Hydrocortisone: every 18 weeks. During this study, blood tests will be performed at the start of therapy, at day 29 post induction and at the time of each intra-thecal therapy (every 18 weeks). Bone marrow biopsy/aspirate will be done days 15 and 29 of induction, then every 6 months until completion.
Interventions
DRUGprednisone
Induction Phase: Given orally on days 1-28
DRUGdoxorubicin
Induction Phase: Given intravenously on day 1 and day 2 CNS Therapy: Given intravenously on day 1 Intensification: Given day 1 of each cycle
DRUGvincristine
Induction: Given intravenously on days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Given intravenously on day 1. Intensification: Given intravenously on day 1 of each cycle. Continuation: Given intravenously on day 1 of each cycle
DRUGmethotrexate
Induction: Given intravenously on day 3. CNS Therapy: Given intrathecally 4 times over two weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intravenously weekly and intrathecally every 18 weeks
DRUGasparaginase
Induction: Given into the muscle on day 5
DRUGdexamethasone
Intensification: Given orally on days 1-5 of each cycle
RADIATIONcranial radiation
Given in 10 daily treatments during CNS therapy phase
DRUGleucovorin
Induction: Given intravenously or orally 36 hours after methotrexate
DRUGcytarabine
Induction: Given intrathecally days 1, 15, 29 CNS Therapy: Given intrathecally 4 times over 2 weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intrathecally every 18 weeks
DRUGhydrocortisone
Induction: Given intrathecally on days 15 and 29. Intensification: Given intrathecally every 18 weeks. Continuation: Given intrathecally every 18 weeks.
CNS Therapy: Taken orally on days 1-14. Intensification: Taken orally on days 1-14. Continuation: Taken orally on days 1-14.
DRUGe. coli L-asparaginase
Intensification: Given in to the muscle weekly.
Sponsors
Brigham and Women's Hospital
Massachusetts General Hospital
Queen Elizabeth II Health Sciences Centre
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have pathologically documented acute lymphoblastic leukemia, excluding mature B-cell ALL. * No prior therapy for leukemia with the following exceptions: * up to one week of steroids; * emergent leukapheresis; * emergency treatment for hyperleukocytosis with hydroxyurea; * cranial RT for CNS leukostasis (one dose only); * emergent radiation therapy to the mediastinum. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. * Between the ages of 18 to 50 years.
Exclusion criteria
* Uncontrolled active infection. * Pregnancy or nursing mothers. * Prior history of pancreatitis. * Prior history of a cerebrovascular accident or hemorrhage. * Evidence of infection with the human immunodeficiency virus. * Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely. * The treating physician should consider all relevant medical and other considerations when deciding whether this protocol is appropriate for a particular patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asparaginase Completion Rate | Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first. | Feasibility based on the rate of asparaginase completion defined as the percentage of patients who, after having achieved a complete remission after induction therapy, complete all 30 doses of asparaginase as part of intensification therapy. Complete remission is defined as peripheral blood without lymphoblasts, a bone marrow with \<5% lymphoblasts, an antigen-presenting cell (APC) \> 1000/mm3, platelets \> 100,000/mm3, and no evidence of extramedullary leukemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 4-year Disease-Free Survival | Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment, (up to 5 years). Relevant for this measure is 4 years from the date of complete remission. | Disease-Free Survival (DFS) based on the Kaplan-Meier method is defined as the time from achieving a complete remission to the first of disease recurrence or death, censored at time of last disease assessment. 4-year DFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from complete remission. Disease relapse is defined as \>25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, fluorescent in situ hybridization (FISH), immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the cerebrospinal fluid (CSF) may qualify as CNS leukemia) also qualifies if confirmed by the PI. |
| 4-year Overall Survival | Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (unless the participant dies or is lost to follow-up). Median follow-up for the whole trial is 4.5 years (95% CI:4.1-5.0 years). | Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death from any cause, and will be censored the date last known alive. 4-year OS is the percent probability of patients remaining alive 4 years from study entry. |
| 4-year Event-Free Survival | Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (unless the participant dies or is lost to follow-up). Median follow-up for the whole trial is 4.5 years (95% CI:4.1-5.0 years). | Event-Free Survival (EFS) based on the Kaplan-Meier method is defined as the time from study entry to the first event of death during induction therapy, failure to achieve CR at the end of induction, death during remission, or relapse. 4-year EFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from study entry. Patients not achieving a CR will be considered events at time zero. EFS will be censored at time of last disease assessment. Disease relapse is defined as \>25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI. |
| Post-Induction Nadir Serum Asparaginase Activity Level | Samples for nadir serum asparaginase activity levels were assayed prior to asparaginase dose given during post-induction, at Weeks 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, and 30. | Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods. |
| Number of Participants With Asparaginase-Related Toxicity | Assessed on an ongoing basis (at least once every 3 months) while patient is on study, and including the treatment phases of Induction, CNS, Intensification, and Continuation. Treatment duration for this study was a median (range) of 507 days (0-1097). | Asparaginase-related toxicity rate is defined as the percentage of patients who experience allergy (all grades), pancreatitis, thrombotic or bleeding complications, bone fracture, or avascular necrosis based on Common Terminology Criteria for Adverse Events (CTCAE) v2. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase prednisone: Induction Phase: Orally days 1-28
doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle
vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43.
CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle
methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks
asparaginase: Induction: Given into the muscle on day 5
dexamethasone: Intensification: Orally days 1-5 of each cycle
cranial radiation: 10 daily treatments during CNS phase
leucovorin: Induction: Intravenously/orally 36 hours after methotrexate
cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks
hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks.
6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14.
e. coli L-asparaginase: Intensification: Given in to the muscle weekly. | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 19 |
| Overall Study | Induction Death | 1 |
| Overall Study | Induction Failure | 10 |
| Overall Study | Ineligible | 8 |
| Overall Study | Relapse | 4 |
| Overall Study | Transplant in first Complete Remission (CR) | 16 |
| Overall Study | Withdrawal by Subject | 3 |
| Overall Study | Withdrew prior to initiating imatinib/Ph+ | 3 |
Baseline characteristics
| Characteristic | Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase |
|---|---|
| Age, Customized 18-29 years | 49 Participants |
| Age, Customized 30-50 years | 51 Participants |
| Central Nervous System (CNS) status at diagnosis CNS 1 (-) CSF WBC <5 without blasts | 83 Participants |
| Central Nervous System (CNS) status at diagnosis CNS 2 (+) CSF WBC <5 with blasts | 6 Participants |
| Central Nervous System (CNS) status at diagnosis CNS 3 (+) CSF WBC >=5 with blasts | 1 Participants |
| Central Nervous System (CNS) status at diagnosis Unknown | 10 Participants |
| Eastern Cooperative Oncology Group (ECOG) Risk classification High Risk (HR) | 58 Participants |
| Eastern Cooperative Oncology Group (ECOG) Risk classification Standard Risk (SR) | 42 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Immunophenotype B-cell | 81 Participants |
| Immunophenotype T-cell | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 5 Participants |
| Race (NIH/OMB) White | 88 Participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 60 Participants |
| White Blood Count (WBC) (x 10^-3) at diagnosis < 20 | 60 Participants |
| White Blood Count (WBC) (x 10^-3) at diagnosis >/= 20 | 39 Participants |
| White Blood Count (WBC) (x 10^-3) at diagnosis Unknown | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 40 / 98 |
| other Total, other adverse events | 0 / 98 |
| serious Total, serious adverse events | 98 / 98 |
Outcome results
Primary
Asparaginase Completion Rate
Feasibility based on the rate of asparaginase completion defined as the percentage of patients who, after having achieved a complete remission after induction therapy, complete all 30 doses of asparaginase as part of intensification therapy. Complete remission is defined as peripheral blood without lymphoblasts, a bone marrow with \<5% lymphoblasts, an antigen-presenting cell (APC) \> 1000/mm3, platelets \> 100,000/mm3, and no evidence of extramedullary leukemia.
Time frame: Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first.
Population: The analysis dataset is comprised of all patients who initiated asparaginase consolidation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Asparaginase Completion Rate | 63 Percentage of patients |
Secondary
4-year Disease-Free Survival
Disease-Free Survival (DFS) based on the Kaplan-Meier method is defined as the time from achieving a complete remission to the first of disease recurrence or death, censored at time of last disease assessment. 4-year DFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from complete remission. Disease relapse is defined as \>25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, fluorescent in situ hybridization (FISH), immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the cerebrospinal fluid (CSF) may qualify as CNS leukemia) also qualifies if confirmed by the PI.
Time frame: Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment, (up to 5 years). Relevant for this measure is 4 years from the date of complete remission.
Population: The analysis dataset is comprised of all eligible patients who achieved a CR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | 4-year Disease-Free Survival | 69 Percent probability |
Secondary
4-year Event-Free Survival
Event-Free Survival (EFS) based on the Kaplan-Meier method is defined as the time from study entry to the first event of death during induction therapy, failure to achieve CR at the end of induction, death during remission, or relapse. 4-year EFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from study entry. Patients not achieving a CR will be considered events at time zero. EFS will be censored at time of last disease assessment. Disease relapse is defined as \>25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI.
Time frame: Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (unless the participant dies or is lost to follow-up). Median follow-up for the whole trial is 4.5 years (95% CI:4.1-5.0 years).
Population: The analysis dataset is comprised of all eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | 4-year Event-Free Survival | 58 Percent probability |
Secondary
4-year Overall Survival
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death from any cause, and will be censored the date last known alive. 4-year OS is the percent probability of patients remaining alive 4 years from study entry.
Time frame: Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (unless the participant dies or is lost to follow-up). Median follow-up for the whole trial is 4.5 years (95% CI:4.1-5.0 years).
Population: The analysis dataset is comprised of all eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | 4-year Overall Survival | 67 Percent probability |
Secondary
Number of Participants With Asparaginase-Related Toxicity
Asparaginase-related toxicity rate is defined as the percentage of patients who experience allergy (all grades), pancreatitis, thrombotic or bleeding complications, bone fracture, or avascular necrosis based on Common Terminology Criteria for Adverse Events (CTCAE) v2.
Time frame: Assessed on an ongoing basis (at least once every 3 months) while patient is on study, and including the treatment phases of Induction, CNS, Intensification, and Continuation. Treatment duration for this study was a median (range) of 507 days (0-1097).
Population: The analysis dataset is comprised of all eligible patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Overall Number of Participants with Pancreatitis | 10 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Overall Number of Participants with Allergy/rash | 5 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Overall Number of Participants with Thrombosis/embolism | 16 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Overall Number of Participants with Bone fracture | 7 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Overall Number of Participants with Avascular necrosis | 5 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Pancreatitis in Induction | 1 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Allergy/rash in Induction | 1 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Thrombosis/embolism in Induction | 1 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Bone fracture in Induction | 0 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Avascular necrosis in Induction | 0 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Pancreatitis in Intensification | 8 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Allergy/rash in Intensification | 4 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Thrombosis/embolism in Intensification | 14 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Bone fracture in Intensification | 3 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Avascular necrosis in Intensification | 2 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Pancreatitis in Continuation | 2 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Allergy/rash in Continuation | 0 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Thrombosis/embolism in Continuation | 2 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Bone fracture in Continuation | 5 participants |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Number of Participants With Asparaginase-Related Toxicity | Number of Participants with Avascular necrosis in Continuation | 4 participants |
Secondary
Post-Induction Nadir Serum Asparaginase Activity Level
Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods.
Time frame: Samples for nadir serum asparaginase activity levels were assayed prior to asparaginase dose given during post-induction, at Weeks 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, and 30.
Population: The analysis dataset is comprised of all eligible patients for whom serum asparaginase activity levels were assayed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 2 NSAA Level | 0 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 4 NSAA Level | 0.047 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 7 NSAA Level | 0.0825 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 10 NSAA Level | 0.088 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 13 NSAA Level | 0.118 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 16 NSAA Level | 0.069 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 19 NSAA Level | 0.075 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 22 NSAA Level | 0.0865 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 25 NSAA Level | 0.0925 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 28 NSAA Level | 0.072 IU/ml |
| Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase | Post-Induction Nadir Serum Asparaginase Activity Level | Week 30 NSAA Level | 0.065 IU/ml |