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International Protocol for the Treatment of Childhood Anaplastic Large Cell Lymphoma


Phase 3
N/A
21 Years
Open (Enrolling)
Both
Lymphoma

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Trial Information

International Protocol for the Treatment of Childhood Anaplastic Large Cell Lymphoma


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.

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.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study within 5.4-6.7
years.

Inclusion 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

PATIENT CHARACTERISTICS:

Age:

- Under 22

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

Hepatic:

- See Disease Characteristics

Renal:

- Not specified

Pulmonary:

- See Disease Characteristics

Immunologic:

- No congenital immunodeficiency

- No AIDS

Other:

- No prior malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- Not specified

Endocrine therapy:

- Prior corticosteroids for anaplastic large cell lymphoma allowed if given for no more
than 8 days

Radiotherapy:

- Not specified

Surgery:

- No prior organ transplantation

Other:

- No other prior therapy for anaplastic large cell lymphoma

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Safety Issue:

No

Principal Investigator

Laurence Brugieres, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Gustave Roussy, Cancer Campus, Grand Paris

Authority:

United States: Federal Government

Study ID:

CDR0000068133

NCT ID:

NCT00006455

Start Date:

December 1999

Completion Date:

Related Keywords:

  • Lymphoma
  • stage I childhood anaplastic large cell lymphoma
  • stage II childhood anaplastic large cell lymphoma
  • stage III childhood anaplastic large cell lymphoma
  • stage IV childhood anaplastic large cell lymphoma
  • recurrent childhood anaplastic large cell lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Anaplastic

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