Acute Lymphoblastic Leukemia
Conditions
Keywords
ALL
Brief summary
The purpose of this study is to determine the safety and effectiveness of a multi-drug chemotherapy regimen in adult patients with Acute Lymphoblastic Leukemia (ALL). We will use a regimen that is often used in pediatric patients and we will add drugs called PEG-asparaginase and E. coli asparaginase. PEG-asparaginase has been given as an injection in the past and has been used in treatment with both children and adults with ALL. Information from those other research studies suggests that intravenous PEG-asparaginase has been administered safely in both children and adults. We hope to gain more information about the participants disease and how it responds to standard chemotherapy drugs used to treat ALL\>
Detailed description
* This study has several periods of treatment called phases and uses several different drugs in each phase. The drugs may be given by mouth, into a vein, or into the spinal fluid (called intrathecal chemotherapy). In some individuals this treatment helps prevent leukemia cells from coming back in the spinal fluid and brain. Radiation therapy will also be administered as part of this treatment regimen. * The treatment program consists of 2-different treatment arms with six separate phases of therapy. The phases of treatment are: (1) Steroid prophase (2) Induction (3) Consolidation I (4) Central nervous system (CNS) therapy (5) Consolidation II (6) Continuation. * The participants treatment arm will depend on the status of their leukemia at the end of the induction therapy (the second phase of treatment). Arm A: all participants who achieve complete remission after Induction and Arm B: all participants who fail to achieve a complete remission after Induction. * Steroid Prophase: All participants are involved in this treatment phase which consists of two drugs, one given intravenously (IV) and one given intrathecally. This phase lasts 3 days and the purpose is to collect scientific data that might be useful in the future and to see how steroids work in treating leukemia * Induction: This phase begins immediately after the steroid prophase and lasts about 1 month. Induction is used to cause a remission. Eight drugs are used during this phase of treatment, and administration is either orally, IV or intrathecal. On day 29, participant's bone marrow and peripheral blood counts will be tested. If they have achieved complete remission or partial remission, they will proceed to the next phase of treatment. If they are not in complete remission, they will receive vincristine by IV on days 32, 39 and 46, until complete remission is achieved. If they do not achieve complete or partial remission by day 53 they will be removed from the study. * Consolidation I: This phase of treatment begins as soon as there is a documented confirmation that the participant's leukemia is either in complete or partial remission. Treatment in this phase lasts about 7 weeks and is intended to further reduce the number of leukemia cells in the body. This consolidation treatment consists of 3 phases: 1A, 1B and 1C. Each phase involves a three week cycle of chemotherapy. Arm A and Arm B will be assigned according to remission status after induction therapy and will determine the order that the participant follows the Consolidation phases. * Central Nervous System (CNS) Therapy: CNS therapy begins 3 weeks after the end of Consolidation I therapy and should last 3 weeks. Treatment includes a series of lumbar punctures with the administration of anti-leukemia drug as well as oral drugs and IV drugs. Radiation therapy will also be given during this phase of therapy. The purpose of radiation therapy is to prevent leukemia from coming back in the brain. Radiation therapy will be given in either 8 or 10 daily treatments. * Consolidation II Therapy: This phase begins as soon as CNS therapy ends and lasts about 27-30 weeks. It consists of cycles of chemotherapy repeated every three weeks along with IV PEG-asparaginase administered every 3 weeks. The cycles will be repeated until the participant receives a total of 10 doses of asparaginase. * Continuation Therapy: This phase begins after the end of the Consolidation II phase. The goal of this phase is to get rid of all leukemia in the body. It consists of cycles of chemotherapy repeated every three weeks and will last until the participant has been in remission for two years. * During all phases of treatment, participants will have tests and procedures to monitor their health and for research purposes.
Interventions
DRUGDoxorubicin
Induction: Intravenously on days 4 and 5. Consolidation 1A: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously day 1 of each cycle.
DRUGCytarabine
Prophase: Intravenously on days 1-3. Induction: Intrathecal on days 15 or 18. Consolidation IB: Intravenously or subcutaneous on days 2-5 and 9-12. Consolidation IC: Intravenously every 12 hours starting on day 1 CNS Therapy: Intrathecal 4 times over 2 weeks. Consolidation II: Intrathecal once every 18 weeks Continuation: Intrathecal every 18 weeks
DRUGMethotrexate
Induction: Intravenously on day 6 and intrathecally on day 29 or 32. Consolidation IA: Intravenously on day 1 and intrathecally on Day 1 (prior to IV). Consolidation IB: Intrathecally on day 1. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation: Intrathecally once every 18 weeks. Continuation: Intravenously weekly and intrathecally every 18 weeks.
DRUGVincristine
Induction: Intravenously on days 4, 11, 18, 25. Consolidation IA: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously on day 1 of each cycle.
DRUGCyclophosphamide
Consolidation IB: Intravenously on day 1
DRUGMethylprednisone
Prophase: Intravenously on days 1-3
Induction: Intrathecally on day 15 or 18. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation II: Intrathecally once every 18 weeks. Continuation: Intrathecally every 18 weeks.
DRUGDexamethasone
Consolidation IC: Orally on days 1-5 twice per day. Consolidation II: Orally on days 1-5 of each cycle. Continuation: Orally on days 1-5 of each cycle.
DRUG6-MP
Induction: Orally on days 3-43 or 33-46. Consolidation IA: orally on days 1-14. Consolidation IB: orally on days 1-14. CNS Therapy: Orally on days 1-14. Consolidation II: Orally on days 1-14. Continuation: Orally on days 1-14 of each cycle.
DRUGPEG-Asparaginase
Consolidation IC: Intravenously every 3 weeks, starting on day 8. CNS Therapy: Intravenously every 3 weeks, starting 3 weeks after the Consolidation IC dose. Consolidation II: Intravenously every 3 weeks.
DRUGImatinib
Used for PH+ ALL subjects enrolled prior to May 1st 2011 only and is used continuously throughout every phase of treatment.
DRUGEtoposide
Consolidation IC: intravenously on days 3, 4 and 5 of this cycle.
PROCEDURERadiation Therapy
Given during CNS Therapy either 8 or 10 daily treatments, on days 1-8 or 1-10, depending upon leukemia involvement in the CSF
Intramuscularly Day 7 of Induction.
Sponsors
Massachusetts General Hospital
Boston Children's Hospital
NCIC Clinical Trials Group
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8) * Age 18.00-50.99 years
Exclusion criteria
* Prior anti-leukemic therapy except 1 week or less of steroids, and/or emergent radiation therapy to the mediastinum, or hydroxyurea or emergent leukopheresis * Known HIV positive * Secondary ALL * Pregnant or breast feeding women * Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely
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 completed defined as the percentage of patients who, after having achieved a complete remission after induction therapy, complete \>25 weeks of IV PEG asparaginase as part of intensification therapy. Complete remission is defined as an interpretable bone marrow (a specimen with normal marrow elements present) with fewer than 5% lymphoblasts and peripheral blood without lymphoblasts, and an antigen presenting cell (APC) \> 1000/mm3 and platelets \> 100,000/mm3, and no evidence of extramedullary leukemia. |
| Number of Participants With Grade 3 or Worse Toxicity. | Assessed on an ongoing basis (at least once every 3 months) while on study, including the treatment phases of Induction, Consolidation I & II, CNS, and Continuation. Treatment duration for this study was a median (range) of 287 days (2-974). | Defined as the number of participants who experience the following grade 3 or worse adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) v3: Neutrophils, Platelets, Febrile neutropenia, Infection, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Bilirubin, Liver dysfunction/failure, Hyperglycemia, Stomatitis, CNS hemorrhage, Thrombosis, Seizure, Osteonecrosis, Hypersensitivity, Pancreatitis, Neuropathy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate | 3-day Steroid prophase and 4-week induction treatment period. Participants are assessed on Day 32 of induction. | Complete remission rate is defined as the percentage of patients with an interpretable bone marrow (a specimen with normal marrow elements present) with fewer than 5% lymphoblasts and peripheral blood without lymphoblasts, and an antigen presenting cell (APC) \> 1000/mm3 and platelets \> 100,000/mm3, and no evidence of extramedullary leukemia. |
| 3-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 3 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. 3-year DFS is the percentage probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 3 years from complete remission. Disease release 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. |
| 3-year Overall 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 3 years from the date of study entry. | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification. | 65 |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification. | 45 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Induction Death | 2 | 0 |
| Overall Study | Induction Failure | 2 | 4 |
| Overall Study | Ineligible | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 9 | 10 |
| Overall Study | Relapse/Progression | 5 | 2 |
| Overall Study | Remission Death | 0 | 1 |
| Overall Study | Transplant in first Complete Remission (CR) | 15 | 6 |
| Overall Study | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Total |
|---|---|---|---|
| Age, Customized 18-19 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Customized 20-29 years | 20 Participants | 18 Participants | 38 Participants |
| Age, Customized 30-39 years | 19 Participants | 11 Participants | 30 Participants |
| Age, Customized 40-50 years | 20 Participants | 13 Participants | 33 Participants |
| Central Nervous System (CNS) status at diagnosis CNS 1 (-) CSF WBC <5 without blasts | 40 Participants | 37 Participants | 77 Participants |
| Central Nervous System (CNS) status at diagnosis CNS 2 (+) CSF WBC <5 with blasts | 4 Participants | 3 Participants | 7 Participants |
| Central Nervous System (CNS) status at diagnosis CNS 3 (+) CSF WBC ≥5 with blasts | 2 Participants | 2 Participants | 4 Participants |
| Central Nervous System (CNS) status at diagnosis Not performed | 2 Participants | 1 Participants | 3 Participants |
| Central Nervous System (CNS) status at diagnosis Traumatic Tap with Blasts | 5 Participants | 0 Participants | 5 Participants |
| Central Nervous System (CNS) status at diagnosis Traumatic Tap without Blasts | 12 Participants | 2 Participants | 14 Participants |
| Eastern Cooperative Oncology Group (ECOG) Risk Classification High Risk (HR) | 34 Participants | 20 Participants | 54 Participants |
| Eastern Cooperative Oncology Group (ECOG) Risk Classification Standard Risk (SR) | 31 Participants | 25 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 37 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 10 Participants |
| Immunophenotype B-cell | 56 Participants | 34 Participants | 90 Participants |
| Immunophenotype T-cell | 9 Participants | 11 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 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 | 5 Participants | 10 Participants | 15 Participants |
| Race (NIH/OMB) White | 58 Participants | 30 Participants | 88 Participants |
| Sex: Female, Male Female | 25 Participants | 18 Participants | 43 Participants |
| Sex: Female, Male Male | 40 Participants | 27 Participants | 67 Participants |
| White Blood Count (WBC) (x10 ^-3) at diagnosis (cells/uL) <30 | 48 Participants | 33 Participants | 81 Participants |
| White Blood Count (WBC) (x10 ^-3) at diagnosis (cells/uL) >=30 | 17 Participants | 11 Participants | 28 Participants |
| White Blood Count (WBC) (x10 ^-3) at diagnosis (cells/uL) Unknown | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 24 / 66 | 12 / 44 |
| other Total, other adverse events | 0 / 66 | 0 / 44 |
| serious Total, serious adverse events | 66 / 66 | 44 / 44 |
Outcome results
Primary
Asparaginase Completion Rate
Feasibility based on the rate of asparaginase completed defined as the percentage of patients who, after having achieved a complete remission after induction therapy, complete \>25 weeks of IV PEG asparaginase as part of intensification therapy. Complete remission is defined as an interpretable bone marrow (a specimen with normal marrow elements present) with fewer than 5% lymphoblasts and peripheral blood without lymphoblasts, and an antigen presenting cell (APC) \> 1000/mm3 and 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) |
|---|---|---|
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Asparaginase Completion Rate | 43 Percentage of patients |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Asparaginase Completion Rate | 79 Percentage of patients |
Primary
Number of Participants With Grade 3 or Worse Toxicity.
Defined as the number of participants who experience the following grade 3 or worse adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) v3: Neutrophils, Platelets, Febrile neutropenia, Infection, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Bilirubin, Liver dysfunction/failure, Hyperglycemia, Stomatitis, CNS hemorrhage, Thrombosis, Seizure, Osteonecrosis, Hypersensitivity, Pancreatitis, Neuropathy.
Time frame: Assessed on an ongoing basis (at least once every 3 months) while on study, including the treatment phases of Induction, Consolidation I & II, CNS, and Continuation. Treatment duration for this study was a median (range) of 287 days (2-974).
Population: The analysis dataset is comprised of all eligible and treated patients for whom toxicity data is reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Neutrophils | 49 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Platelets | 44 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Febrile neutropenia | 30 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Infection with grade 3/4 neutropenia | 24 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Infection, other | 5 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | AST | 19 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | ALT | 34 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Bilirubin | 24 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Liver dysfunction/failure | 2 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Hyperglycemia | 10 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Stomatitis | 8 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | CNS hemorrhage | 2 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Thrombosis | 19 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Seizure | 5 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Osteonecrosis | 4 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Hypersensitivity | 3 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Pancreatitis | 1 participants |
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Neuropathy | 5 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Seizure | 0 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Neutrophils | 31 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Hyperglycemia | 8 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Platelets | 30 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Neuropathy | 4 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Febrile neutropenia | 23 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Stomatitis | 2 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Infection with grade 3/4 neutropenia | 10 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Osteonecrosis | 1 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Infection, other | 3 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | CNS hemorrhage | 0 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | AST | 5 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Pancreatitis | 2 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | ALT | 13 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Thrombosis | 7 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Bilirubin | 3 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Hypersensitivity | 6 participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Number of Participants With Grade 3 or Worse Toxicity. | Liver dysfunction/failure | 1 participants |
Secondary
3-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. 3-year DFS is the percentage probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 3 years from complete remission. Disease release 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 3 years from the date of complete remission.
Population: The analysis dataset is comprised of all eligible patients who achieved a complete remission.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | 3-year Disease Free Survival | 70 Percentage of patients |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | 3-year Disease Free Survival | 75 Percentage of patients |
Secondary
3-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.
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 3 years from the date of study entry.
Population: The analysis dataset is comprised of all eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | 3-year Overall Survival | 70 Percentage of patients |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | 3-year Overall Survival | 83 Percentage of patients |
Secondary
Complete Remission Rate
Complete remission rate is defined as the percentage of patients with an interpretable bone marrow (a specimen with normal marrow elements present) with fewer than 5% lymphoblasts and peripheral blood without lymphoblasts, and an antigen presenting cell (APC) \> 1000/mm3 and platelets \> 100,000/mm3, and no evidence of extramedullary leukemia.
Time frame: 3-day Steroid prophase and 4-week induction treatment period. Participants are assessed on Day 32 of induction.
Population: The analysis dataset is comprised of all patients who are evaluable for complete remission
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pre-amendment Cohort, 2500 IU/m2 q2 Weeks | Complete Remission Rate | 57 Participants |
| Post-amendment Cohort, 2000 IU/m2 q3 Weeks | Complete Remission Rate | 34 Participants |