Overview

This trial is active, not recruiting.

Condition lymphoma
Treatments asparaginase, cyclophosphamide, cytarabine, daunorubicin hydrochloride, dexamethasone, doxorubicin hydrochloride, leucovorin calcium, mercaptopurine, methotrexate, prednisone, thioguanine, vincristine sulfate, radiation therapy
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date June 2000
End date August 2008
Trial size 393 participants
Trial identifier NCT00004228, A5971, CCG-59701, CCG-59701C, CCG-A5971, CDR0000067470, POG-A5971

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Doxorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Methotrexate, Intrathecal Methotrexate)
asparaginase E.coli L-asparaginase
Given IV
cyclophosphamide Cytoxan
Given IV
cytarabine cytosine arabinoside
Given IV
daunorubicin hydrochloride daunomycin
Given IV
dexamethasone Decadron
Given IV
doxorubicin hydrochloride Adriamycin
Given IV
mercaptopurine 6-MP
Given IV
methotrexate MTX
Given IV
prednisone Deltasone
Given IV
thioguanine 6-thioguanine
Given PO
vincristine sulfate Oncovin
Given IV
(Experimental)
Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, doxorubicin hydrochloride, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, prednisone, Methotrexate, Intrathecal Methotrexate)
asparaginase E.coli L-asparaginase
Given IV
cyclophosphamide Cytoxan
Given IV
cytarabine cytosine arabinoside
Given IV
daunorubicin hydrochloride daunomycin
Given IV
dexamethasone Decadron
Given IV
doxorubicin hydrochloride Adriamycin
Given IV
mercaptopurine 6-MP
Given IV
methotrexate MTX
Given IV
prednisone Deltasone
Given IV
thioguanine 6-thioguanine
Given PO
vincristine sulfate Oncovin
Given IV
(Experimental)
Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, daunorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate)
asparaginase E.coli L-asparaginase
Given IV
cyclophosphamide Cytoxan
Given IV
cytarabine cytosine arabinoside
Given IV
daunorubicin hydrochloride daunomycin
Given IV
dexamethasone Decadron
Given IV
doxorubicin hydrochloride Adriamycin
Given IV
mercaptopurine 6-MP
Given IV
methotrexate MTX
Given IV
prednisone Deltasone
Given IV
thioguanine 6-thioguanine
Given PO
vincristine sulfate Oncovin
Given IV
(Experimental)
Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, daunorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate)
asparaginase E.coli L-asparaginase
Given IV
cyclophosphamide Cytoxan
Given IV
cytarabine cytosine arabinoside
Given IV
daunorubicin hydrochloride daunomycin
Given IV
dexamethasone Decadron
Given IV
doxorubicin hydrochloride Adriamycin
Given IV
leucovorin calcium LCV
Given IV
mercaptopurine 6-MP
Given IV
methotrexate MTX
Given IV
prednisone Deltasone
Given IV
thioguanine 6-thioguanine
Given PO
vincristine sulfate Oncovin
Given IV
radiation therapy
(Experimental)
Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, doxorubicin hydrochloride, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate)
asparaginase E.coli L-asparaginase
Given IV
cyclophosphamide Cytoxan
Given IV
cytarabine cytosine arabinoside
Given IV
daunorubicin hydrochloride daunomycin
Given IV
dexamethasone Decadron
Given IV
doxorubicin hydrochloride Adriamycin
Given IV
leucovorin calcium LCV
Given IV
mercaptopurine 6-MP
Given IV
methotrexate MTX
Given IV
prednisone Deltasone
Given IV
thioguanine 6-thioguanine
Given PO
vincristine sulfate Oncovin
Given IV
(Experimental)
Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, daunorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate)
asparaginase E.coli L-asparaginase
Given IV
cyclophosphamide Cytoxan
Given IV
cytarabine cytosine arabinoside
Given IV
daunorubicin hydrochloride daunomycin
Given IV
dexamethasone Decadron
Given IV
doxorubicin hydrochloride Adriamycin
Given IV
leucovorin calcium LCV
Given IV
mercaptopurine 6-MP
Given IV
methotrexate MTX
Given IV
prednisone Deltasone
Given IV
thioguanine 6-thioguanine
Given PO
vincristine sulfate Oncovin
Given IV
(Experimental)
Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, doxorubicin hydrochloride, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate)
asparaginase E.coli L-asparaginase
Given IV
cyclophosphamide Cytoxan
Given IV
cytarabine cytosine arabinoside
Given IV
daunorubicin hydrochloride daunomycin
Given IV
dexamethasone Decadron
Given IV
doxorubicin hydrochloride Adriamycin
Given IV
leucovorin calcium LCV
Given IV
mercaptopurine 6-MP
Given IV
methotrexate MTX
Given IV
prednisone Deltasone
Given IV
thioguanine 6-thioguanine
Given PO
vincristine sulfate Oncovin
Given IV

Primary Outcomes

Measure
Event-free Survival
time frame: 5 years

Secondary Outcomes

Measure
Percentage of Patients With Overall Survival as Assessed by Time to Death
time frame: 5 years

Eligibility Criteria

Male or female participants from 1 year up to 30 years old.

DISEASE CHARACTERISTICS: - Newly diagnosed disseminated lymphoblastic lymphoma or localized lymphoblastic lymphoma* - Less than 25% tumor cells in the bone marrow - Previously untreated (prior intrathecal cytarabine allowed if protocol therapy begins within 72 hours) - Stage III or IV disease - NOTE: *Localized lymphoblastic lymphoma is closed to accrual as of 10/2005 PATIENT CHARACTERISTICS: Age: - 1 to 30 Performance status: - Not specified Life expectancy: - Not specified Hematopoietic: - Not specified Hepatic: - Not specified Renal: - Not specified Cardiovascular: - Adequate cardiac function PRIOR CONCURRENT THERAPY: Biologic therapy: - Not specified Chemotherapy: - See Disease Characteristics Endocrine therapy: - Emergency steroid therapy (if required) must be started within 72 hours prior to protocol therapy Radiotherapy: - Emergency radiotherapy (if required) must be started within 72 hours prior to protocol therapy Surgery: - Not specified Other: - No other prior therapy except for emergency treatment of airway obstruction and/or superior vena cava syndrome

Additional Information

Official title Randomized Phase III Study for the Treatment of Newly Diagnosed Disseminated Lymphoblastic Lymphoma or Localized Lymphoblastic Lymphoma
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Children's Oncology Group.