Acute Lymphocytic Leukemia
Conditions
Keywords
Acute Lymphocytic Leukemia, Leukemia
Brief summary
The purpose of this research study is to identify better ways to treat children and young adults with acute lymphocytic leukemia (ALL). At the same time, doctors hope to define methods to identify those patients at higher risk for certain side effects, as well as those who are at higher risk for relapse of their leukemia.
Detailed description
Outline of Therapy: Combinations of chemotherapy drugs will be given orally, intravenously and intrathecally (directly into the cerebrospinal fluid by spinal tap) over a period of roughly two and a half years. Therapy will be divided into five phases: Induction (4 weeks): chemotherapy given to produce a clinical remission (defined by normal blood counts, with the absence of leukemia cells in the blood and fewer than 5% leukemia cells in the bone marrow). Consolidation (11 weeks): chemotherapy given to consolidate the remission. Delayed Intensification (7 weeks) Intensive chemotherapy aimed at killing any resistant leukemia cells will be given only for patients at high risk of relapse. Intensive Continuation (approximately 1 year): Eight week cycles of chemotherapy, given eight times. Continuation (final year of therapy): Eight week cycles of largely oral chemotherapy, with one clinic visit for a lumbar puncture every eight weeks. Irradiation: radiation will be given in the middle of intensive continuation to the head and spine of those patients who have leukemia cells found in the cerebrospinal fluid at the time of diagnosis. Follow-up: After the conclusion of therapy, there will be periodic office visits, initially monthly, then gradually spaced out to annual visits. The purpose of these visits is to evaluate for late side-effects of therapy.
Interventions
DRUGaminopterin
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGL-asparaginase
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGcyclophosphamide
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGcytarabine
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGdaunomycin
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGdexamethasone
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUG6-mercaptopurine
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGmethotrexate
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUG6-thioguanine
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGvincristine
Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation
DRUGTriple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone)
DRUGLeucovorin
Sponsors
National Cancer Institute (NCI)
Rutgers, The State University of New Jersey
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: * Newly Diagnosed ALL, excluding mature B-cell ALL (surface Ig positive) * Patients with overt CNS (central nervous system) or testicular disease are eligible * Informed consent according to institutional and FDA guidelines. * Adequate organ function is required. * HIV seropositive patients will not be excluded from this study. * Patients greater than 1 year of age and less than 29.99 years of age are eligible.
Exclusion criteria
* Patients with medical, psychological, or psychiatric problems that are likely to compromise their ability to tolerate intensive therapy will be ineligible. * All patients with evidence of significant organ dysfunction not thought to be attributable to ALL (patients with clinically significant congestive heart failure, cardiac ejection fraction \<40%, total bilirubin \>2, serum creatinine \>2) will be ineligible. Note: echocardiogram or MUGA are required prior to therapy ONLY for those patients with history or physical findings suggestive of cardiac dysfunction not directly attributable to anemia or ALL. Note: Patients with total bilirubin \>2 but direct (conjugated) bilirubin less than the upper limit of normal will still be eligible. These patients should be evaluated for deficiency of the enzyme glucuronyl transferase.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With ALL at High Risk of Relapse (Arm 2) Who Were Relapse-free at 5 Years | 5 years | This measure looks at the percentage of patients on Arm 2 who did not experience a relapse at 5 years, where relapse is defined as the presence of progressive disease after the achievement of a complete remission. |
Secondary
| Measure | Time frame |
|---|---|
| To Measure 5-methyltetrahydrofolate, Aminopterin and Methotrexate Uptake in Leukemic Blasts Isolated at Diagnosis | 5 years |
Countries
United States
Participant flow
Recruitment details
59 patients with ALL were enrolled between March, 2001 and September, 2005 at the Cancer Institute of New Jersey (outpatient clinical research facility) and 1 patient was enrolled at Jersey Shore University Medical Center (a community hospital).
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Standard Risk 6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin | 21 |
| Arm 2 High Risk 6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C | 39 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Consolidation (12 Weeks) | Adverse Event | 0 | 1 |
| Consolidation (12 Weeks) | Lack of Efficacy | 0 | 2 |
| Consolidation (12 Weeks) | Not documented | 0 | 1 |
| Consolidation (12 Weeks) | Patient moved to another state | 0 | 1 |
| Induction (4 Weeks) | Death | 1 | 2 |
| Induction (4 Weeks) | Lack of Efficacy | 0 | 1 |
| Induction (4 Weeks) | Withdrawal by Subject | 0 | 2 |
| Intensive Continuation (8X8-week Cycles) | Death | 1 | 0 |
| Intensive Continuation (8X8-week Cycles) | Lack of Efficacy | 0 | 3 |
Baseline characteristics
| Characteristic | Arm 2 High Risk | Arm 1 Standard Risk | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 30 Participants | 21 Participants | 51 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 0 Participants | 9 Participants |
| Age, Continuous | 16 years STANDARD_DEVIATION 9.8 | 3.71 years STANDARD_DEVIATION 1.77 | 11.7 years STANDARD_DEVIATION 9.89 |
| Region of Enrollment United States | 39 participants | 21 participants | 60 participants |
| Sex: Female, Male Female | 18 Participants | 11 Participants | 29 Participants |
| Sex: Female, Male Male | 21 Participants | 10 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 21 | 39 / 39 |
| serious Total, serious adverse events | 20 / 21 | 36 / 39 |
Outcome results
Primary
Percentage of Patients With ALL at High Risk of Relapse (Arm 2) Who Were Relapse-free at 5 Years
This measure looks at the percentage of patients on Arm 2 who did not experience a relapse at 5 years, where relapse is defined as the presence of progressive disease after the achievement of a complete remission.
Time frame: 5 years
Population: Number of high risk ALL patients treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2 High Risk | Percentage of Patients With ALL at High Risk of Relapse (Arm 2) Who Were Relapse-free at 5 Years | 64.9 percentage of participants |
Secondary
To Measure 5-methyltetrahydrofolate, Aminopterin and Methotrexate Uptake in Leukemic Blasts Isolated at Diagnosis
Time frame: 5 years
Population: We did not analyze this outcome measure. The laboratory analysis was not performed. The Principal Investigator left the institution.