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Phase III Randomized Study of Induction and Maintenance Chemotherapy Regimens With Different Doses and Schedules of Methotrexate From the Berlin-Frankfurt-Munster-K2 Protocol With or Without Vinblastine in Children With Anaplastic Large Cell Lymphoma
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information
Alternate Title
Combination Chemotherapy in Treating Children With Anaplastic Large Cell Lymphoma
Basic Trial Information
| Phase | Type | Status | Age | Protocol IDs |
|---|
| Phase III | Treatment | Active | Under 22 | FRE-IGR-ALCL99
EU-20031, NHL2000/06, NCT00006455 |
Objectives - Compare the event-free survival in children with anaplastic large cell lymphoma treated with various induction and maintenance chemotherapy regimens with or without vinblastine.
- Compare the impact of different doses and schedules of methotrexate from the Berlin-Frankfurt-Munster-K2 Protocol in terms of overall survival, complete remission rate, CNS relapse rate, and nonlymphoma-related death and early death rates in these patients.
Entry Criteria Disease Characteristics:
- Histologically proven standard-risk (SR) or high-risk (HR) anaplastic
large
cell lymphoma
- SR disease defined by no involvement of the skin,
mediastinum, liver, spleen, or lung
- HR disease defined by any of the following:
- Biopsy proven skin lesions (except skin lesions
overlying an involved node
or isolated skin disease)
- Mediastinal involvement by x-ray or CT scan
- Involvement of the liver (enlarged by at least 5 cm
and/or nodular), spleen (enlarged and/or nodular), or lung (biopsy not
needed for obvious lesions)
- Histologic or cytologic slides must be available for national pathology
review for all patients not meeting the classical criteria for diagnosis
(typical histopathology, immunohistochemistry: CD30 positive, endomysial
antibody positive, nucleophosmin negative, anaplastic lymphoma kinase
(ALK)
positive (if available), null or T-immunophenotype) unless proven t(2;5)
- Must enroll within 1 week prior to beginning study regimen A
- No CNS involvement (CSF or cerebral tumor)
- First randomization (SR or HR disease):
- Must have begun prephase therapy
- No isolated primary skin disease
- No low-risk disease defined as completely resected
stage I disease
- Second randomization (HR disease only):
- Must have completed first randomization therapy
without disease progression
Prior/Concurrent Therapy:
Biologic therapy: Chemotherapy: Endocrine therapy: - Prior corticosteroids for anaplastic large cell lymphoma
allowed if given for no more than 8 days
Radiotherapy: Surgery: - No prior organ transplantation
Other: - No other prior therapy for anaplastic large cell
lymphoma
Patient Characteristics:
Age: Performance status: Life expectancy: Hematopoietic: - See Disease Characteristics
Hepatic: - See Disease Characteristics
Renal: Pulmonary: - See Disease Characteristics
Immunologic: - No congenital immunodeficiency
- No AIDS
Other: Expected Enrollment 400A total of 400 patients will be accrued for this study within 5.4-6.7 years. Outcomes Primary Outcome(s)Event-free survival
Secondary Outcome(s)Overall survival
Complete remission achieved after treatment course B3 and lasting ≥ 4 weeks
Short- and long-term toxicity
Nonlymphoma related death and early deaths (excluding deaths occurring after second-line treatment for failure or relapse)
CNS relapses
Outline This is a randomized, multicenter study. Patients are stratified
according to country, vinblastine (VBL) (yes vs no), and prognostic factors
(standard-risk (SR) vs high-risk (HR) disease). Beginning immediately after confirmation of diagnosis, patients receive
prephase therapy comprising dexamethasone (DM) IV or orally daily on days 1
and 2 and every 12 hours on days 3-5; cyclophosphamide (CTX) IV over 1 hour on
days 1 and 2; and methotrexate (MTX) intrathecally (IT), doxorubicin (DOX) IV,
and hydrocortisone (HC) IT on day 1. Patients are then assigned to one of two treatment groups based on
prognosis: - Group 1 (SR disease): Patients are randomized to arm I or III:
- Arm I: Patients receive
treatment on arm I as defined below on day 1, and then the following courses
as defined below in the following order beginning on day 6: A1, B1, A2, B2,
A3, and B3.
- Arm III: Patients receive treatment on arm III as defined below on
day 1, and then the following courses as defined below in the following order
beginning on day 6: regimen AM1, BM1, AM2, BM2, AM3, and BM3.
- Group 2 (HR disease):
- First randomization: Patients are randomized to arm I or III:
- Arm I:
Patients receive treatment on arm I as defined below on day 1 and then course
A1 as defined below on day 6.
- Arm III: Patients receive treatment on arm III
as defined below on day 1 and then course AM1 as defined below on day 6.
- Second randomization: Patients without disease progression after
completion of the above therapy are randomized to arm I, II, III, or IV.
- Arm
I: Patients receive treatment on arm I as defined below on day 1, and then the
following courses as defined below in the following order after blood counts
recover: B1, A2, B2, A3, and B3.
- Arm II: Patients receive treatment on arm II
as defined below on day 1, and then the following courses as defined below in
the following order after blood counts recover: BV1, AV2, BV2, AV3, and BV3.
- Arm III: Patients receive treatment on arm III as defined below on day 1, and
then the following courses as defined below in the following order after blood
counts recover: BM1, AM2, BM2, AM3, and BM3.
- Arm IV: Patients receive
treatment on arm IV as defined below on day 1, and then the following courses
as defined below in the following order after blood counts recover: BMV1,
AMV2, BMV2, AMV3, and BMV3.
Patients are followed every 2 months for 1 year, every 4 months for 2
years, every 6 months for 2 years, and then annually thereafter. DEFINITIONS: - Arms I-IV are defined below:
- Arm I: Patients receive lower dose MTX IV over 24 hours and MTX IT.
- Arm II: Patients receive lower dose MTX IV over 24 hours and MTX IT.
Patients with HR disease also receive VBL IV weekly for 1 year beginning 3
weeks after initiation of course BV3.
- Arm III: Patients receive higher dose MTX IV over 3 hours without
intrathecal therapy.
- Arm IV: Patients receive treatment as in arm III. Patients with HR
disease also receive VBL IV weekly for 1 year beginning 3 weeks after
initiation of course BMV3.
- Regimens A, B, AV, BV, AM, BM, AMV, and BMV are defined below:
- Regimen A (courses A1, A2, and A3): Patients receive DM IV or orally
every 12 hours on days 1-5; MTX IV over 24 hours on day 1; MTX IT, DOX IV and
HC IT (beginning 2-4 hours after initiation of MTX infusion) on day 1;
leucovorin calcium (CF) IV rescue at 42, 48, and 54 hours after initiation of
MTX infusion; ifosfamide (IFF) IV over 1 hour on days 1-5 (before initiation
of MTX infusion); cytarabine (ARA-C) IV over 1 hour every 12 hours and
etoposide (VP-16) IV over 2 hours once (beginning after completion of ARA-C
infusion) on days 4 and 5. Each course lasts 3 weeks.
- Regimen B (courses B1, B2, and B3): Patients receive DM, MTX,
intrathecal therapy, and CF rescue as in regimen A. Patients also receive CTX
IV over 1 hour on days 1-5 and DOX IV over 1 hour on days 4 and 5. Each
course lasts 3 weeks.
- Regimen AV (courses AV1, AV2, and AV3): Patients receive treatment as in
regimen A and VBL IV on day 1. Each course lasts 3 weeks.
- Regimen BV (courses BV1, BV2, and BV3): Patients receive treatment as in
regimen B and VBL IV as in regimen AV. Each course lasts 3 weeks.
- Regimen AM (courses AM1, AM2, and AM3): Patients receive DM IV or orally
every 12 hours on days 1-5; MTX IV over 3 hours on day 1; and CF IV rescue
every 6 hours for a total of 12 doses beginning 24 hours after initiation of
MTX infusion. Patients also receive IFF, ARA-C, and VP-16 as in regimen A.
Each course lasts 3 weeks.
- Regimen BM (courses BM1, BM2, and BM3): Patients receive CTX and DOX as
in regimen B. Patients also receive DM, MTX, and CF rescue as in regimen AM.
Each course lasts 3 weeks.
- Regimen AMV (courses AMV1, AMV2, and AMV3): Patients receive treatment
as in regimen AM and VBL as in regimen AV. Each course lasts 3 weeks.
- Regimen BMV (courses BMV1, BMV2, and BMV3): Patients receive treatment
as in regimen BM and VBL as in regimen AV. Each course lasts 3 weeks.
Trial Contact Information
Trial Lead Organizations Institut Gustave Roussy | | | | Laurence Brugieres, MD, Protocol chair | | | |
Trial Sites
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| Austria |
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Vienna |
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| | | | St. Anna Children's Hospital |
| | | Helmut Gadner, MD, FRCPG | |
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| Belgium |
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Leuven |
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| | | | U.Z. Gasthuisberg |
| | | Anne Uyttebroeck, MD | |
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| France |
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Villejuif |
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| | | | Institut Gustave Roussy |
| | | Laurence Brugieres, MD | |
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| Germany |
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Giessen |
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| | | | Kinderklinik |
| | | Alfred Reiter, MD | |
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| Italy |
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Padova |
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| | | | Azienda Ospedaliera di Padova |
| | | Angelo Rosolen, MD | |
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| Netherlands |
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Den Haag |
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| | | | Dutch Childhood Leukemia Study Group |
| | | Inge Appel, MD | |
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| Spain |
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Valencia |
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| | | | Hospital Clinico Universitario de Valencia |
| | | Rafael Delgado, MD | |
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| Sweden |
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Stockholm |
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| | | | Karolinska University Hospital - Huddinge |
| | | Olle Bjork, MD | |
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| Switzerland |
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Zurich |
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| | | | University Children's Hospital |
| | | Felix Niggli, MD | |
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| United Kingdom |
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| England |
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Cambridge |
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| | | | | Addenbrooke's Hospital |
| | | Denise Williams, MD | |
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| Registry Information | | | Official Title | | International Protocol for the Treatment of Childhood Anaplastic Large Cell Lymphoma | | | Trial Start Date | | 1999-12-01 | | | Registered in ClinicalTrials.gov | | NCT00006455 | | | Date Submitted to PDQ | | 2000-07-06 | | | Information Last Verified | | 2008-02-12 |
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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