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Phase III Randomized Study of Four Chemotherapy Regimens in Children or Adolescents With Newly Diagnosed Disseminated Stage III or IV Lymphoblastic Lymphoma or Localized Lymphoblastic Lymphoma (Closed to Accrual as of 10/2005)
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information
Alternate Title
Combination Chemotherapy in Treating Children or Adolescents With Newly Diagnosed Stage III or Stage IV Lymphoblastic Lymphoma
Basic Trial Information
| Phase | Type | Status | Age | Protocol IDs |
|---|
| Phase III | Treatment | Completed | 1 to 30 | COG-A5971
CCG-59701, CCG-59701C, CCG-A5971, POG-A5971, NCT00004228, A5971 |
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] Entry Criteria 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 lymphblastic lymphoma is closed to accrual as of 10/2005]
Prior/Concurrent Therapy:
Biologic therapy: 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: Other: - No other prior therapy except for emergency treatment of
airway obstruction and/or superior vena cava syndrome
Patient Characteristics:
Age: Performance status: Life expectancy: Hematopoietic: Hepatic: Renal: Cardiovascular: - Adequate cardiac function
Expected Enrollment 400Approximately 250-400 patients will be accrued for this study within 5 years. Outcomes Primary Outcome(s)Event-free survival as assessed by time to treatment failure, occurrence of second malignant neoplasm, or death from any cause
Secondary Outcome(s)Survival as assessed by time to death
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. Published ResultsAbromowitch M, Termuhlen A, Chang M, et al.: High-dose methotrexate and early intensification of therapy do not improve 3 year EFS in children and adolescents with disseminated lymphoblastic lymphoma: results of the randomized arms of COG A5971. [Abstract] Blood 112 (11): A-3610, 2008. Smock KJ, Nelson M, Tripp SR, et al.: Characterization of childhood precursor T-lymphoblastic lymphoma by immunophenotyping and fluorescent in situ hybridization: a report from the Children's Oncology Group. Pediatr Blood Cancer 51 (4): 489-94, 2008.[PUBMED Abstract] Coustan-Smith E, Abromowitz M, Sandlund JT, et al.: A novel approach for minimal residual disease detection in childhood T-cell lymphoblastic lymphoma (T-LL): a Children’s Oncology Group report. [Abstract] Blood 110 (11): A-3564, 2007.
Trial Contact Information
Trial Lead Organizations Children's Oncology Group | | | | Minnie Abromowitch, MD, Protocol chair | | | |
| Registry Information | | | Official Title | | Randomized Phase III Study for the Treatment of Newly Diagnosed Disseminated Lymphoblastic Lymphoma or Localized Lymphoblastic Lymphoma | | | Trial Start Date | | 2000-06-15 | | | Trial Completion Date | | 2008-08-25 | | | Registered in ClinicalTrials.gov | | NCT00004228 | | | Date Submitted to PDQ | | 1999-12-10 | | | Information Last Verified | | 2007-07-28 | | | NCI Grant/Contract Number | | CA13539 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
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