Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT00558519
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia.
- Detailed Description
OUTLINE: This is a multicenter study. The purpose of this study is to improve the outcome of adolescents and young adults with acute lymphoblastic leukemia (ALL). The objectives of the study are described below.
OBJECTIVES:
* To describe the outcomes (i.e., complete response rate, event-free survival, disease-free survival \[DFS\], and overall survival \[OS\]) of adolescents and young adults with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a pediatric chemotherapy regimen by adult hematologists/oncologists at multiple sites.
* To explore the feasibility of extending the "pediatric approach" to adult patients up to 40 years of age.
* To estimate the DFS and OS of these patients.
* To describe the toxicities observed in these patients.
* To compare the outcomes of patients treated on this protocol with appropriate similar patients (by age and disease characteristics) treated by pediatric oncologists on protocol COG-AALL0232.
* To evaluate the adherence of adult hematologists/oncologists and their patients to a "pediatric" ALL treatment regimen and identify reasons for variances.
* To analyze and describe the outcomes of patients treated on this study according to pretreatment characteristics such as age, gender, white blood cell count, other hematologic parameters, blood chemistry, immunophenotype, cytogenetics and molecular genetic characteristics, and treatment variables such as treatment site (academic center or community), and protocol adherence.
* To analyze and describe the outcomes of patients treated on this study according to baseline psychosocial characteristics, demographics, and family support.
The courses of treatment for the research study are described below.
* Remission induction therapy: Patients receive intrathecal (IT) cytarabine on day 1; vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally twice daily on days 1-28; daunorubicin hydrochloride IV on days 1, 8, 15, and 22; pegaspargase IV or intramuscularly (IM) on day 4 or 5 or 6; and IT methotrexate on days 8 and 29\*. Patients undergo bone marrow aspirate (BMA) and biopsy on day 29 to assess induction response and minimal residual disease status. Patients with M1 marrow (\< 1% lymphoblasts) proceed to remission consolidation therapy. Patients with M2 marrow (\> 5% but \< 25% lymphoblasts) proceed to extended remission induction therapy. Patients with M3 marrow are removed from protocol therapy.
NOTE: \*Patients with CNS3 disease also receive IT methotrexate on days 15 and 22.
* Extended remission induction therapy: Patients receive prednisone IV or orally twice daily on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM or IV on day 4 or 5 or 6; and daunorubicin hydrochloride IV on day 1. Patients undergo BMA and biopsy on day 15. Patients with M1 marrow proceed to remission consolidation therapy. Patients with M2 or M3 bone marrow are removed from protocol therapy.
* Remission consolidation therapy: Patients receive cyclophosphamide IV on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM or IV on days 15 and 43; and IT methotrexate on days 1, 8, 15\*, and 22\*. Once blood counts recover, patients proceed to interim maintenance therapy.
NOTE: \*Patients with CNS3 disease do not receive IT methotrexate on days 15 and 22.
* Interim maintenance therapy: Patients receive vincristine IV and methotrexate (Capizzi methotrexate) IV on days 1, 11, 21, 31, and 41; pegaspargase IM or IV on days 2 and 22; and IT methotrexate on days 1 and 31. Once blood counts recover (ANC ≥ 750/mm\^3 and platelet count ≥ 75,000/mm\^3), patients proceed to delayed intensification therapy.
* Delayed intensification therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or orally twice daily on days 1-7 and 15-21; doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV on day 4 or 5 or 6 AND day 43; cyclophosphamide IV on day 29; cytarabine IV or SC on days 29-32 and 36-39; oral thioguanine on days 29-42; and IT methotrexate on days 1, 29, and 36. Once blood counts recover, patients proceed to maintenance therapy.
* Maintenance therapy: Patients receive vincristine IV on days 1, 29, and 57; dexamethasone IV or orally twice daily on days 1-5, 29-33, and 57-61; mercaptopurine orally on days 1-84; IT methotrexate on day 1\*; and oral methotrexate on days 8, 15, 22, 29\*\*, 36, 43, 50, 57, 64, 71, and 78.
Treatment repeats every 12 weeks for 2 years from the start of interim maintenance (for female patients) or 3 years from the start of interim maintenance (for male patients).
NOTE: \*IT methotrexate is also given on day 29 of the first 4 courses of maintenance therapy.
NOTE: \*\*Oral methotrexate is held on day 29 of the first 4 courses of maintenance therapy (when IT methotrexate is given).
* Radiotherapy: During the first course of maintenance therapy, patients with testicular disease undergo concurrent radiotherapy to the testes 5 days a week for 2.5 weeks (total dose 2400 cGy given in 12 daily fractions); patients with CNS3 disease undergo concurrent cranial radiotherapy 5 days a week for 2 weeks (total dose of 1800 cGy given in 10 daily fractions); and patients with T-cell ALL undergo concurrent cranial radiotherapy (total dose of 2400 cGy given in 10 daily fractions) 5 days a week for 2 weeks.
Patients may complete surveys at the end of courses 1, 2, and 4, at the end of all protocol treatment, and at 6 and 18 months after the end of all protocol treatment.
After completion of study treatment, patients are followed every 1-3 months for 3 years and then every 6 months for 7 years.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 318
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (chemotherapy, radiotherapy) cyclophosphamide Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) cytarabine Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) daunorubicin hydrochloride Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) dexamethasone Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) mercaptopurine Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) vincristine sulfate Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) radiation therapy Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) doxorubicin hydrochloride Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) methotrexate Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) pegaspargase Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information. Treatment (chemotherapy, radiotherapy) thioguanine Patients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information.
- Primary Outcome Measures
Name Time Method Complete Response Rate Up to 8 years post-registration Complete response rate is defined as the percentage of patients who achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) at the end of induction therapy.
Event-free Survival Up to 8 years post-registration EFS was defined as time from registration in this study to the earliest occurrence of any of the following: failure to achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) by day 60, death, relapse at any site, or development of second malignant disease.
Disease-free Survival Up to 8 years post-registration DFS was defined as time from bone marrow response in this study to the earliest occurrence of any of the following: failure to achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) by day 60, death, relapse at any site, or development of second malignant disease.
Overall Survival Up to 8 years post-registration OS was defined from registration to death resulting from any cause.
Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity) Up to 10 years post-registration The number of participants who experienced toxicity (defined as at least one grade 3 or higher adverse event at least possibly related to treatment) is reported below.
- Secondary Outcome Measures
Name Time Method