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 survivalAcute 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
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