Treatment of Childhood Acute Lymphoblastic Leukemia
Overview[ - collapse ][ - ]
| Purpose | The purpose of this study is to reduce the side-effects and discomfort of anti-leukemia therapy, to attain long-term control of the disease and to hopefully eradicate it. |
|---|---|
| Condition | Acute Lymphoblastic Leukemia |
| Intervention | Drug: asparaginase (E. Coli) Drug: asparaginase (Erwina) Drug: dexrazoxane Drug: doxorubicin Procedure: cranial radiation (once daily fractionation) Procedure: cranial radiation (twice-daily fractionation) Procedure: Intrathecal chemotherapy without radiation |
| Phase | Phase 3 |
| Sponsor | Dana-Farber Cancer Institute |
| Responsible Party | Dana-Farber Cancer Institute |
| ClinicalTrials.gov Identifier | NCT00165087 |
| First Received | September 9, 2005 |
| Last Updated | December 20, 2007 |
| Last verified | December 2007 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 9, 2005 |
|---|---|
| Last Updated Date | December 20, 2007 |
| Start Date | January 1996 |
| Estimated Primary Completion Date | September 2006 |
| Current Primary Outcome Measures |
|
| Current Secondary Outcome Measures | -To compare randomized treatment groups using health-related quality of life analyses. |
Descriptive Information[ + expand ][ + ]
| Brief Title | Treatment of Childhood Acute Lymphoblastic Leukemia |
|---|---|
| Official Title | Treatment of Childhood Acute Lymphoblastic Leukemia |
| Brief Summary | The purpose of this study is to reduce the side-effects and discomfort of anti-leukemia therapy, to attain long-term control of the disease and to hopefully eradicate it. |
| Detailed Description | - Children with acute lymphoblastic leukemia (ALL) are treated somewhat differently depending upon on the relative risk of the leukemia recurring. For this study they are classified into "Standard Risk", "High Risk" and "Infant/High Risk". - The treatment for patients in the "Standard Risk" and "High Risk" groups consists of three phases of therapy: induction treatment; prevention of brain and spinal cord leukemia (CNS treatment); and intensification/continuation chemotherapy. - The treatment for patients in the "Infant/High Risk" group consists of four phases of therapy: induction treatment; infant intensification therapy; intensification/continuation chemotherapy; and CNS treatment. - The induction treatment consists of a combination of chemotherapy drugs whose purpose is to kill all detectable leukemia cells. This process usually requires a least one month and includes six anti-leukemia drugs. These drugs are: vincristine, doxorubicin, methotrexate, cytosine arabinoside, asparaginase and steroids (methylprednisolone or prednisone). - After the induction phase, "Infant/High Risk" patients will receive a highly intensive month of treatment (infant intensification) . Drugs used during this month include high-dose methotrexate, asparaginase, 6-mercaptopurine and high dose cytosine arabinoside (ARA-C). - CNS treatment begins during induction therapy but is intensified during the second and third month after diagnosis. Treatment for all patients will include a series of spinal taps with the instillation of anti-leukemia drugs, including cytosine arabinoside and methotrexate and with or without hydrocortisone (depending upon randomization). - All high risk patients (those in both "High Risk" and "Infant/High Risk") as well as some standard risk patients will receive radiation treatment to the brain. Radiation therapy will either be given in either "conventional" treatments (once daily for 10 days), or "hyperfractionated" treatments (twice daily at half doses for 10 days). Total dose of radiation is 1800 cGy. - Intensification and continuation therapy, begins 4-5 weeks after diagnosis for "Standard Risk" and "High Risk" groups and 4-5 weeks after infant intensification in "Infant/High Risk" group. This phase of treatment continues until the completion of two years of treatment. Patients in the "Standard Risk" group will receive five anti-leukemia drugs (vincristine, prednisone, methotrexate, asparaginase, and 6-mercaptopurine). Patients in "High Risk" and "Infant/High Risk" will receive six anti-leukemia drugs (vincristine, prednisone, doxorubicin, methotrexate, asparaginase and 6-mercaptopurine). - All patients will be able to participate in a randomization comparing two types of asparaginase, E.coli and Erwinia. Patients will be randomized to receive either once weekly E.coli or once-weekly Erwinia during the Intensification phase, each given for a total of 20 weeks. - Patients in the "Standard Risk" group are able to participate in an additional randomization. Standard risk patients will be randomized to receive one of two different regimens designed to prevent central nervous system leukemia, either 1)radiation therapy (given twice daily) with chemotherapy in the spinal fluid every 18 weeks, or 2) intensive chemotherapy in the spinal fluid alone without radiation. - Patients in the "High Risk" and "Infant/High Risk" groups are able to participate in two randomizations in addition to the asparaginase randomization. The first will be to assess whether the drug dexrazoxane prevents heart damage caused by doxorubicin without affecting risk of relapse. Patients will be randomized to receive either doxorubicin alone or doxorubicin with dexrazoxane during the induction, CNS and intensification phases. The second randomization will compare the relative efficacy and toxicity of different cranial radiation schedules. Patients will be randomized to receive radiation in either once daily or twice daily fractions. - Blood and bone marrow samples will be collected to learn more about the biology of leukemia. These samples will also be used to test minimal residual disease levels to learn if these levels help predict risk of relapse. - Quality of life questionnaires will also be performed by the parents of patients, by children over eight, and by the child's clinician. |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Acute Lymphoblastic Leukemia |
| Intervention | Drug: asparaginase (E. Coli) Drug: asparaginase (Erwina) Drug: dexrazoxane Drug: doxorubicin Procedure: cranial radiation (once daily fractionation) Procedure: cranial radiation (twice-daily fractionation) Procedure: Intrathecal chemotherapy without radiation |
| Study Arm (s) | Not Provided |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Terminated |
|---|---|
| Estimated Enrollment | 491 |
| Estimated Completion Date | September 2006 |
| Estimated Primary Completion Date | September 2006 |
| Eligibility Criteria | Inclusion Criteria: - Acute lymphoblastic leukemia, excluding known mature B-cell ALL - < 18 years of age - Patients who are leukopheresed or exchanged are eligible for study only after completion of the pheresis or exchange transfusion - Absence of a t(8,14) (q24; q32), t (8,22), t(2,8) - Total bilirubin < 1.4mg/dl Exclusion Criteria: - Known HIV positive - Prior steroid therapy within 30 days of diagnosis - Septic shock - Ongoing intracranial hemorrhage - Clinical evidence of CNS or lung leukostasis |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Canada, Puerto Rico |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00165087 |
|---|---|
| Other Study ID Numbers | 95-001 |
| Has Data Monitoring Committee | Not Provided |
| Information Provided By | Dana-Farber Cancer Institute |
| Study Sponsor | Dana-Farber Cancer Institute |
| Collaborators | Children's Hospital Boston |
| Investigators | Principal Investigator: Stephen E. Sallan, MD Dana-Farber Cancer Institute |
| Verification Date | December 2007 |
Locations[ + expand ][ + ]
| Ochsner Clinic | New Orleans, Louisiana, United States, 70121 |
|---|---|
| Maine Medical Center | Lewiston, Maine, United States, 04240 |
| Dana-Farber Cancer Institute | Boston, Massachusetts, United States, 02115 |
| Children's Hospital Boston | Boston, Massachusetts, United States, 02115 |
| Mt. Sinai Medical Center | New York, New York, United States, 10029 |
| University of Rochester | Rochester, New York, United States, 14627 |
| McMaster University | Hamilton, Ontario, Canada |
| Sainte Justine Hosptial | Montreal, Quebec, Canada |
| Laval University | Montreal, Quebec, Canada |
| San Jorge Children's Hospital | Santurce, Puerto Rico, 00912 |