NCT00004228

Combination Chemotx in Treating Children or Adolescents With Newly Diagnosed Stg III or Stg IV Lymphoblastic Lymphoma

Randomized Phase III Study for the Treatment of Newly Diagnosed Disseminated Lymphoblastic Lymphoma or Localized Lymphoblastic Lymphoma

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 393 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which regimen of combination chemotherapy is most effective for lymphoblastic lymphoma. PURPOSE: This randomized phase III trial is studying different regimens of combination chemotherapy to compare how well they work in treating children or adolescents with newly diagnosed stage III or stage IV lymphoblastic lymphoma.

Detailed description

OBJECTIVES: * Compare the event-free survival and overall survival of children or adolescents with newly diagnosed disseminated stage III or IV lymphoblastic lymphoma treated with 4 chemotherapy regimens\*. * Determine whether treatment with a regimen without methotrexate maintains the same disease-free survival as NHL/BFM 90 in these patients. * Determine whether intensification with anthracycline and cyclophosphamide improves disease-free survival in these patients. * Collect outcome data on uniformly treated patients with localized disease or CNS-positive disease. * Determine whether rapid reduction in tumor volume by chest radiography and CT scan is predictive of improved outcome in patients treated with these regimens. * Determine the prevalence of bone marrow involvement at presentation in these patients. * Determine whether peripheral blood can replace bone marrow in the initial staging of these patients. * Determine the clinical significance of bone marrow and peripheral blood involvement in these patients. NOTE: \*All patients as of 4/2006 receive treatment on Arm III regimen only OUTLINE: Patients are stratified by disease characteristics (disseminated lymphoblastic lymphoma vs localized lymphoblastic lymphoma \[localized lymphoblastic lymphoma is closed to accrual as of 10/2005\]) and age. Patients with CNS negative disseminated lymphoblastic lymphoma are randomized to 1 of 4 treatment arms\*. Patients with testicular involvement at diagnosis are nonrandomly assigned to arm IV and do not receive testicular radiotherapy. Patients with localized lymphoblastic lymphoma (closed to accrual as of 10/2005) are not randomized. NOTE: \*All patients as of 4/2006 receive treatment on Arm III only * Localized lymphoblastic lymphoma (closed to accrual as of 10/2005): * Induction (5 weeks): Patients receive vincristine IV and daunorubicin IV over 15 minutes to 2 hours on days 0, 7, 14, and 21; oral prednisone on days 0-27; and asparaginase intramuscularly (IM) on days 3, 5, and 7 and then 3 times a week for 9 doses (during days 8-21). Patients also receive methotrexate intrathecally (IT) on days 7 and 28 and cytarabine IT on day 0. * Consolidation (5 weeks): Patients receive methotrexate IT on days 0, 7, 14, and 21 followed by cyclophosphamide IV over 1 hour on days 0 and 14; cytarabine IV on days 0-3, 7-10, 14-17, and 21-24; oral mercaptopurine on days 0-27; and oral prednisone over 10 days. * Interim maintenance (8 weeks): Patients receive methotrexate IT on days 0 and 28; oral mercaptopurine on days 0-41; and oral methotrexate on days 7, 14, 21, and 35. * Delayed intensification (7 weeks): Patients receive vincristine IV and doxorubicin IV over 15 minutes to 2 hours on days 0, 7, and 14; asparaginase IM on day 3 and then 3 times a week for 6 doses; oral dexamethasone on days 0-30; cyclophosphamide IV over 1 hour on day 28; and cytarabine IV or SC on days 28-31 and 35-38. Patients also receive oral thioguanine on days 28-41 and methotrexate IT on days 28 and 35. * Maintenance (84 day course): Patients receive vincristine IV on days 0, 28, and 56; oral prednisone on days 0-4, 28-32, and 56-60; oral methotrexate on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; oral mercaptopurine on days 0-83; and methotrexate IT on day 0. * Disseminated lymphoblastic lymphoma: * Arm I (closed to accrual as of 4/2006): Patients receive same induction, consolidation, and interim maintenance therapy schedule as localized lymphoblastic lymphoma patients. * Delayed intensification (7 weeks): Patients receive vincristine IV and doxorubicin IV over 15 minutes to 2 hours on days 0, 7, 14, and 21; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-28. Patients also receive cyclophosphamide IV over 1 hour on day 35; cytarabine IV or SC on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. * Maintenance (84 day course): Patients receive same therapy as localized lymphoblastic lymphoma patients, except methotrexate IT is administered on day 0 and 28 (for first 4 courses). * Arm II (closed to accrual as of 4/2006): Patients receive consolidation, interim maintenance, and maintenance therapy as in arm I. * Induction (5 weeks): Patients receive vincristine IV on days 0, 7, 14, and 21; daunorubicin IV over 48 hours on days 0-2; oral prednisone on days 0-27; and asparaginase IM on days 3, 5, and 7 and then 3 times a week for 9 doses (during days 8-21). Patients also receive methotrexate IT on days 7 and 28; cyclophosphamide IV over 1 hour on day 2; and cytarabine IT on day 0. * Delayed intensification (7 weeks): Patients receive vincristine IV on days 0, 7, 14, 21; daunorubicin IV over 48 hours on days 0-2; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-28. Patients also receive cyclophosphamide IV over 1 hour on days 2 and 35; cytarabine IV or SC on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. * Arm III: * Induction (5 weeks): Patients receive vincristine IV and daunorubicin IV over 1 hour on days 0, 7, 14, and 21 and oral prednisone on days 0-37. Patients also receive asparaginase IM on day 11 and then 3 times a week for 9 doses; methotrexate IT on days 7 and 28; and cytarabine IT on day 0. * Consolidation (5 weeks): Patients receive methotrexate IT and cyclophosphamide IV over 1 hour on days 0 and 14; cytarabine IV or SC on days 0-3, 7-10, 14-17, and 21-24; oral mercaptopurine on days 0-27; and oral prednisone over 10 days. * Interim maintenance (9 weeks): Patients receive methotrexate IT and IV on days 7, 21, 35, and 49; oral mercaptopurine on days 0-55; and leucovorin calcium IV at 42, 48, and 54 hours after methotrexate IV. * Delayed intensification (10 weeks): Patients receive vincristine IV and doxorubicin IV over 1 hour on days 0, 7, 14, and 21; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-29. Patients also receive cyclophosphamide IV over 1 hour on day 35; cytarabine IV on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. * Maintenance (84 day courses): Patients receive vincristine IV on days 0, 28, and 56; oral prednisone on days 0-4, 28-32, and 56-60; oral methotrexate on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and oral mercaptopurine on days 0-83. * Arm IV (closed to accrual as of 4/2006): Patients receive consolidation and interim maintenance therapy as in arm III. * Induction: Patients receive vincristine IV on days 0, 7, 14, and 21; daunorubicin IV over 48 hours on days 0-2; oral prednisone on days 0-37; asparaginase IM on day 11 and then 3 times a week for 9 doses; methotrexate IT on days 7, 14, 21, and 28; cyclophosphamide IV on day 2; and cytarabine IT on day 0. * Delayed intensification (10 weeks): Patients receive vincristine IV on days 7, 14, 21, and 28; daunorubicin IV over 48 hours on days 0-2; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-29. Patients also receive cyclophosphamide IV over 1 hour on days 2 and 35; cytarabine IV on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. * Maintenance (84 day courses): Patients receive therapy as in arm III. Patients who are over 1 year of age and have CNS disease at diagnosis undergo cranial radiotherapy once daily 5 days a week beginning on day 0. Patients over 2 years of age undergo radiotherapy over 11-14 days (6-9 days for 1-2 years of age). Patients are followed monthly for one year, every 3 months for 1 year, every 6 months for 1.5 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 250-400 patients will be accrued for this study within 5 years.

Conditions

• Lymphoma

Interventions

Type	Name	Description
DRUG	asparaginase	Given IV
DRUG	cyclophosphamide	Given IV
DRUG	cytarabine	Given IV
DRUG	daunorubicin hydrochloride	Given IV
DRUG	dexamethasone	Given IV
DRUG	doxorubicin hydrochloride	Given IV
DRUG	leucovorin calcium	Given IV
DRUG	mercaptopurine	Given IV
DRUG	methotrexate	Given IV
DRUG	prednisone	Given IV
DRUG	thioguanine	Given PO
DRUG	vincristine sulfate	Given IV
RADIATION	radiation therapy

Timeline

• Start date: 2000-06-01
• Primary completion: 2008-08-01
• Completion: 2015-03-31
• First posted: 2003-01-27
• Last updated: 2019-08-06
• Results posted: 2013-12-05

Locations

176 sites across 5 countries: United States, Australia, Canada, Puerto Rico, Switzerland