Prednisolone or Dexamethasone Combined With Chemotherapy in Treating Young Patients With Newly Diagnosed Lymphoblastic Lymphoma

NCT ID: NCT00275106

Last Updated: 2013-07-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2012-08-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as prednisolone and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known whether prednisolone is more effective than dexamethasone when given together with combination chemotherapy in treating lymphoblastic lymphoma.

PURPOSE: This phase III randomized clinical trial is studying prednisolone to see how well it works compared to dexamethasone when given together with combination chemotherapy in treating young patients with newly diagnosed lymphoblastic lymphoma.

Detailed Description

OBJECTIVES:

Primary

• Compare the event-free survival of young patients with newly diagnosed lymphoblastic lymphoma treated with induction prednisolone vs dexamethasone.
• Compare the safety of standard maintenance treatment over 18 months vs 24 months in these patients.

Secondary

• Determine prognostic factors highly predicative for treatment failure in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

• Cytoreductive prephase: All patients receive methotrexate intrathecally (IT) once on day 1 and prednisolone IV or orally 3 times daily on days 1-7.
• Induction phase (part 1): Patients with T-cell lymphoblastic lymphoma (T-LBL) are randomized to 1 of 2 induction treatment arms. Patients with LBL with an unknown immunophenotype are assigned to arm I. Patients with precursor B-cell lymphoblastic lymphoma (pB-LBL) are assigned to arm II.

• Arm I (T-LBL or LBL with an unknown immunophenotype): Patients receive prednisolone IV or orally 3 times daily on days 8-28; vincristine IV and daunorubicin hydrochloride IV over 1 hour on days 8, 15, 22, and 29; asparaginase IV over 1 hour on days 12, 15, 18, 21, 24, 27, 30, and 33; and methotrexate IT on days 12 and 33; Patients with CNS involvement receive additional methotrexate IT on days 18 and 27. Patients then proceed to part 2 of the induction phase.
• Arm II (T-LBL or pB-LBL): Patients receive dexamethasone IV or orally 3 times daily on days 8-28. Patients also receive vincristine, daunorubicin hydrochloride, asparaginase, and methotrexate as in arm I. Patients then proceed to part 2 of the induction phase.
• Induction phase (part 2): Patients receive cyclophosphamide IV over 1 hour on days 36 and 64; cytarabine IV on days 38-41, 45-48, 52-55, and 59-62; oral mercaptopurine on days 36-63; and methotrexate IT on days 45 and 59. Two weeks later, patients proceed to protocol M.
• Protocol M: Patients receive oral mercaptopurine once daily on days 1-56 and high-dose methotrexate IV continuously over 24 hours, and methotrexate IT on days 8, 22, 36, and 50. Patients also receive leucovorin calcium IV 42, 48, and 54 hours after the start of high-dose methotrexate infusion. Patients are then stratified according to stage of disease (I or II vs III or IV). Patients with stage I or II disease proceed directly to maintenance therapy 2 weeks after completion of protocol M. Patients with stage III or IV disease proceed to the re-induction phase 2 weeks after completion of protocol M.
• Re-induction phase: Patients receive dexamethasone IV or orally 3 times daily on days 1-21; vincristine IV and doxorubicin hydrochloride IV over 1 hour on days 8, 15, 22, and 29; asparaginase IV over 1 hour on days 8, 11, 15, and 18; cyclophosphamide IV over 1 hour on day 36; cytarabine IV on days 38-41 and 45-48; oral thioguanine on days 36-49; and methotrexate IT on days 38 and 45. Patients proceed to maintenance therapy 2 weeks after completion of the re-induction phase.
• Maintenance therapy: Patients with T-LBL are randomized to 1 of 2 maintenance treatment arms. Patients with pB-LBL or LBL with an unknown immunophenotype are assigned to arm I. Any patients with evidence of initial CNS involvement undergo cranial radiotherapy before starting maintenance therapy. Patients must show no evidence of progressive disease before starting maintenance therapy.

• Arm I: Patients receive oral mercaptopurine once a day and oral methotrexate once a week for up to 2 years (from the first day of the cytoreductive phase) in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive treatment as in arm I for up to 1½ years (from the first day of the cytoreductive phase) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: Approximately 600 patients will be accrued for this study.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

asparaginase

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

mercaptopurine

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

prednisolone

Intervention Type: DRUG

thioguanine

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

radiation therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed lymphoblastic lymphoma (LBL)

• Stage I-IV disease
• T-cell LBL, precursor B-cell LBL, or LBL with an unknown immunophenotype

PATIENT CHARACTERISTICS:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No known HIV or AIDS infection
• No severe immunodeficiency
• No other prior malignancy
• No prior disease that would preclude treatment with chemotherapy

PRIOR CONCURRENT THERAPY:

• More than 2 months since prior systemic corticosteroids for a duration of > 8 days
• No prior chemotherapy
• No prior radiotherapy
• No prior organ transplant
• No trimethoprim-sulfamethoxazole 6 days before or during methotrexate therapy
• No concurrent participation in another clinical trial

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Inter-group Cooperation on Childhood and Adolescent Non Hodgkin Lymphoma

OTHER

Sponsor Role: collaborator

Children's Cancer and Leukaemia Group

OTHER

Sponsor Role: lead

Principal Investigators

Robert F. Wynn, MD

Role: STUDY_CHAIR

Royal Manchester Children's Hospital

Tim O.B. Eden, MB, BS, FRCPE, FRCP, FRCPCH, F

Role:

The Christie NHS Foundation Trust

Alfred Reiter, MD

Role: STUDY_CHAIR

University Hospital Erlangen

Locations

Kinderklinik

Giessen, , Germany

Our Lady's Hospital for Sick Children Crumlin

Dublin, , Ireland

Birmingham Children's Hospital

Birmingham, England, United Kingdom

Institute of Child Health at University of Bristol

Bristol, England, United Kingdom

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Leicester Royal Infirmary

Leicester, England, United Kingdom

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Royal London Hospital

London, England, United Kingdom

Great Ormond Street Hospital for Children

London, England, United Kingdom

Royal Manchester Children's Hospital

Manchester, England, United Kingdom

Sir James Spence Institute of Child Health

Newcastle upon Tyne, England, United Kingdom

Queen's Medical Centre

Nottingham, England, United Kingdom

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Children's Hospital - Sheffield

Sheffield, England, United Kingdom

Southampton General Hospital

Southampton, England, United Kingdom

Royal Marsden - Surrey

Sutton, England, United Kingdom

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Royal Hospital for Sick Children

Edinburgh, Scotland, United Kingdom

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Childrens Hospital for Wales

Cardiff, Wales, United Kingdom

Countries

Germany; Ireland; United Kingdom

References

Landmann E, Burkhardt B, Zimmermann M, Meyer U, Woessmann W, Klapper W, Wrobel G, Rosolen A, Pillon M, Escherich G, Attarbaschi A, Beishuizen A, Mellgren K, Wynn R, Ratei R, Plesa A, Schrappe M, Reiter A, Bergeron C, Patte C, Bertrand Y. Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma. Haematologica. 2017 Dec;102(12):2086-2096. doi: 10.3324/haematol.2015.139162. Epub 2017 Oct 5.

Reference Type: DERIVED

PMID: 28983060 (View on PubMed)

Other Identifiers

CDR0000454508

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU-20598

Identifier Type: -

Identifier Source: secondary_id

CCLG-EURO-LIB-02

Identifier Type: -

Identifier Source: secondary_id

EICNHL-ERURO-LB02

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2004-0011861-17

Identifier Type: -

Identifier Source: secondary_id

CCLG-NHL-2004-08

Identifier Type: -

Identifier Source: org_study_id