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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Lymphoma

Intervention: asparaginase (Drug); cyclophosphamide (Drug); cytarabine (Drug); daunorubicin hydrochloride (Drug); dexamethasone (Drug); doxorubicin hydrochloride (Drug); leucovorin calcium (Drug); mercaptopurine (Drug); methotrexate (Drug); prednisolone (Drug); thioguanine (Drug); vincristine sulfate (Drug); radiation therapy (Procedure)

Phase: Phase 3

Status: Terminated

Sponsored by: Children's Cancer and Leukaemia Group

Official(s) and/or principal investigator(s):
Robert F. Wynn, MD, Study Chair, Affiliation: Royal Manchester Children's Hospital
Tim O.B. Eden, MB, BS, FRCPE, FRCP, FRCPCH, F, Affiliation: Christie Hospital NHS Foundation Trust
Alfred Reiter, MD, Study Chair, Affiliation: Kinderklinik

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.

Clinical Details

Official title: Treatment Protocol for T-Cell and B-Precursor Cell Lymphoblastic Lymphoma of the European Inter-group Co-operation on Childhood Non-Hodgkin-Lymphoma (EICNHL)

Study design: Allocation: Randomized, Primary Purpose: Treatment

Primary outcome: Conditional event-free survival

Secondary outcome:

Overall survival

Acute and long-term toxicity

Non-lymphoma-related deaths and early deaths (excluding deaths occurring after second line treatment for failure or relapse)

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.

Eligibility

Minimum age: N/A. Maximum age: 21 Years. Gender(s): Both.

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

Locations and Contacts

Kinderklinik, Giessen D-35385, Germany

Our Lady's Hospital for Sick Children Crumlin, Dublin 12, Ireland

Birmingham Children's Hospital, Birmingham, England B4 6NH, United Kingdom

Institute of Child Health at University of Bristol, Bristol, England BS2 8AE, United Kingdom

Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom

Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom

Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom

Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England L12 2AP, United Kingdom

Great Ormond Street Hospital for Children, London, England WC1N 3JH, United Kingdom

Royal London Hospital, London, England E1 1BB, United Kingdom

Royal Manchester Children's Hospital, Manchester, England M27 4HA, United Kingdom

Sir James Spence Institute of Child Health, Newcastle-Upon-Tyne, England NE1 4LP, United Kingdom

Queen's Medical Centre, Nottingham, England NG7 2UH, United Kingdom

Oxford Radcliffe Hospital, Oxford, England 0X3 9DU, United Kingdom

Children's Hospital - Sheffield, Sheffield, England S10 2TH, United Kingdom

Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom

Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom

Royal Belfast Hospital for Sick Children, Belfast, Northern Ireland BT12 6BE, United Kingdom

Royal Aberdeen Children's Hospital, Aberdeen, Scotland AB25 2ZG, United Kingdom

Royal Hospital for Sick Children, Edinburgh, Scotland EH9 1LF, United Kingdom

Royal Hospital for Sick Children, Glasgow, Scotland G3 8SJ, United Kingdom

Childrens Hospital for Wales, Cardiff, Wales CF14 4XW, United Kingdom

Additional Information

Starting date: September 2004
Last updated: July 9, 2013

Page last updated: August 23, 2015

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