CINJALL: Treatment for Children With Acute Lymphocytic Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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CINJALL: Treatment for Children With Acute Lymphocytic Leukemia

Conditions
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Acute Lymphocytic Leukemia

Intervention / Treatment
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* Drug: aminopterin
* Drug: L-asparaginase
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: daunomycin
* Drug: dexamethasone
* Drug: 6-mercaptopurine
* Drug: methotrexate
* Drug: 6-thioguanine
* Drug: vincristine
* Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone)
* Drug: Leucovorin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 Standard Risk<br>6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin | Drug: L-asparaginase<br>* 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<br>Drug: daunomycin<br>* 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<br>Drug: dexamethasone<br>* 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<br>Drug: 6-mercaptopurine<br>* 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<br>Drug: methotrexate<br>* 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<br>Drug: vincristine<br>* 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<br>Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone)<br> <br> Drug: Leucovorin<br> <br> |
| Experimental: Arm 2 High Risk<br>6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C | Drug: aminopterin<br>* 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<br>Drug: L-asparaginase<br>* 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<br>Drug: cyclophosphamide<br>* 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<br>Drug: cytarabine<br>* 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<br>Drug: daunomycin<br>* 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<br>Drug: dexamethasone<br>* 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<br>Drug: 6-mercaptopurine<br>* 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<br>Drug: 6-thioguanine<br>* 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<br>Drug: vincristine<br>* 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<br>Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone)<br> <br> Drug: Leucovorin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Measure 5-methyltetrahydrofolate, Aminopterin and Methotrexate Uptake in Leukemic Blasts Isolated at Diagnosis |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lymphocytic Leukemia, Leukemia