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NCT00006455 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Children With Anaplastic Large Cell Lymphoma (ALCL 99)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2022-05-31

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for treating anaplastic large cell lymphoma. PURPOSE: This randomized phase III trial is studying several different regimens of combination chemotherapy to compare how well they work in treating children with anaplastic large cell lymphoma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility 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
healthy Volunteers
false
maximum Age
21 Years
minimum Age
0 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
interventions
  1. name
    cyclophosphamide
    type
    DRUG
  2. name
    cytarabine
    type
    DRUG
  3. name
    dexamethasone
    type
    DRUG
  4. name
    doxorubicin hydrochloride
    type
    DRUG
  5. name
    etoposide
    type
    DRUG
  6. name
    ifosfamide
    type
    DRUG
  7. name
    leucovorin calcium
    type
    DRUG
  8. name
    methotrexate
    type
    DRUG
  9. name
    therapeutic hydrocortisone
    type
    DRUG
  10. name
    vinblastine sulfate
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
SINGLE_GROUP
primary Purpose
TREATMENT
Enrollment
count
885
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Event-free survival
secondary Outcomes
  1. measure
    Overall survival
  2. measure
    Complete remission achieved after treatment course B3 and lasting ≥ 4 weeks
  3. measure
    Short- and long-term toxicity
  4. measure
    Nonlymphoma related death and early deaths (excluding deaths occurring after second-line treatment for failure or relapse)
  5. measure
    CNS relapses
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for treating anaplastic large cell lymphoma. PURPOSE: This randomized phase III trial is studying several different regimens of combination chemotherapy to compare how well they work in treating children with anaplastic large cell lymphoma.
detailed Description
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.
Source references
references
  1. citation
    Attarbaschi A, Mann G, Rosolen A, Williams D, Uyttebroeck A, Marky I, Lamant L, Horibe K, Wrobel G, Beishuizen A, Wossmann W, Reiter A, Mauguen A, Le Deley MC, Brugieres L; European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) ALCL99 Trial. Limited stage I disease is not necessarily indicative of an excellent prognosis in childhood anaplastic large cell lymphoma. Blood. 2011 May 26;117(21):5616-9. doi: 10.1182/blood-2010-12-324012. Epub 2011 Mar 28.
    pmid
    21444917
    type
    RESULT
  2. citation
    Wrobel G, Mauguen A, Rosolen A, Reiter A, Williams D, Horibe K, Brugieres L, Le Deley MC; European Inter-Group for Childhood, Non-Hodgkin Lymphoma (EICNHL). Safety assessment of intensive induction therapy in childhood anaplastic large cell lymphoma: report of the ALCL99 randomised trial. Pediatr Blood Cancer. 2011 Jul 1;56(7):1071-7. doi: 10.1002/pbc.22940. Epub 2011 Jan 28.
    pmid
    21280197
    type
    RESULT
  3. citation
    Le Deley MC, Rosolen A, Williams DM, Horibe K, Wrobel G, Attarbaschi A, Zsiros J, Uyttebroeck A, Marky IM, Lamant L, Woessmann W, Pillon M, Hobson R, Mauguen A, Reiter A, Brugieres L. Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial. J Clin Oncol. 2010 Sep 1;28(25):3987-93. doi: 10.1200/JCO.2010.28.5999. Epub 2010 Aug 2.
    pmid
    20679620
    type
    RESULT
Source notices and limitations
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        ith MDD results include the following:<div class="pdq-content-list"><ul id="_2006"><li>Among 74 patients treated on the NHL-BFM-95 and <a href="/clinicaltrials/NCT00006455">ALCL99 (NCT00006455)</a> trials, 16 patients with more than 10 NCNs <em class="gene-name">NPM</em>::<em class="gene-name">ALK</em> in bone marrow had a cumula
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        de the following:<div class="pdq-content-list"><ul id="_2006"><li>Among 74 patients treated on the NHL-BFM-95 and <a href="/clinicaltrials/NCT00006455">ALCL99 (NCT00006455)</a> trials, 16 patients with more than 10 NCNs <em class="gene-name">NPM</em>::<em class="gene-name">ALK</em> in bone marrow had a cumulative incidence of rel
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        div> <p id="_2396" tabindex="-1"> In a cohort of Japanese patients with anaplastic large cell lymphoma who were treated on the <a href="/clinicaltrials/NCT00006455">ALCL99 (NCT00006455)</a> study, comparable results were obtained for a three-category risk classification algorithm.[<a href="#cit/section_1.45">45</a>] For a
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        2396" tabindex="-1"> In a cohort of Japanese patients with anaplastic large cell lymphoma who were treated on the <a href="/clinicaltrials/NCT00006455">ALCL99 (NCT00006455)</a> study, comparable results were obtained for a three-category risk classification algorithm.[<a href="#cit/section_1.45">45</a>] For a cohort of 180 patien
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        s of 375 children and adolescents with systemic <em class="gene-name">ALK</em>-positive anaplastic large cell lymphoma enrolled on the <a href="/clinicaltrials/NCT00006455">ALCL99 (NCT00006455)</a> study, the presence of a small cell or lymphohistiocytic component was observed in 32% of patients. This finding was significantly a
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        adolescents with systemic <em class="gene-name">ALK</em>-positive anaplastic large cell lymphoma enrolled on the <a href="/clinicaltrials/NCT00006455">ALCL99 (NCT00006455)</a> study, the presence of a small cell or lymphohistiocytic component was observed in 32% of patients. This finding was significantly associated with a high
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        52 weeks, and the cumulative dose of doxorubicin is 300 mg/m<span class="sup">2</span>. No alkylator therapy is given.</li><li><strong><a href="/clinicaltrials/NCT00006455">FRE-IGR-ALCL99</a>:</strong> Dexamethasone, cyclophosphamide, ifosfamide, etoposide, doxorubicin, intravenous (IV) methotrexate (3 g/m<span class="sup">2</spa
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      8. context exact
        for patients with large cell lymphoma (anaplastic large cell lymphoma and diffuse large B-cell lymphoma). </li></ul></div></li><li>The <a href="/clinicaltrials/NCT00006455">FRE-IGR-ALCL99</a> trial used three cycles of chemotherapy after cytoreductive prophase for patients with stage I, completely resected disease. The therapy fo
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        ; return(false);">Level of evidence A1</a>] Building on these results, the European Intergroup for Childhood NHL group conducted the <a href="/clinicaltrials/NCT00006455">FRE-IGR-ALCL99</a> study (based on the GER-GPOH-NHL-BFM-90 regimen). <div class="pdq-content-list"><ul id="_1666"><li>First, this randomized study demonstrate
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        ] </li><li>One arm of the COG <a href="/clinicaltrials/NCT01979536">ANHL12P1 (NCT01979536)</a> study added brentuximab vedotin to the <a href="/clinicaltrials/NCT00006455">ALCL99</a> trial chemotherapy backbone, and 68 patients were enrolled.[<a href="#cit/section_8.25">25</a>]<div class="pdq-content-list"><ul id="_2427"><li>Pat
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        37; 63%) who had a 5-year EFS rate of 84.9%.</li></ul></div> </li><li>The second arm of the COG ANHL12P1 study added crizotinib to the <a href="/clinicaltrials/NCT00006455">ALCL99</a> trial chemotherapy backbone, and 66 patients were enrolled.[<a href="#cit/section_8.26">26</a>]<div class="pdq-content-list"><ul id="_2488"><li>Pat
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      1. context
        Updated: April 17, 2025
        datetime
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    Preserved source evidence · Not medical advice