A Study in Adults With Untreated Acute Lymphoblastic Leukemia
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT00136435
- Lead Sponsor
- Dana-Farber Cancer Institute
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Only Arm for this study prednisone Only Arm for this study Only Arm for this study vincristine Only Arm for this study Only Arm for this study doxorubicin Only Arm for this study Only Arm for this study methotrexate Only Arm for this study Only Arm for this study asparaginase Only Arm for this study Only Arm for this study dexamethasone Only Arm for this study Only Arm for this study cranial radiation Only Arm for this study Only Arm for this study leucovorin Only Arm for this study Only Arm for this study cytarabine Only Arm for this study Only Arm for this study e. coli L-asparaginase Only Arm for this study Only Arm for this study hydrocortisone Only Arm for this study Only Arm for this study 6-mercaptopurine (6-MP) Only Arm for this study
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Related Research Topics
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Trial Locations
- Locations (12)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University Of Columbia Medical Center
🇺🇸New York, New York, United States
Manitoba Blood & Marrow Transplant Program CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
McMaster University Medical Center
🇨🇦Hamilton, Ontario, Canada
Queen's University
🇨🇦Kingston, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Hospital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
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