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...
Date First Received: January 10, 2006
Last Updated: May 23, 2008
Verified by: National Cancer Institute (NCI), April 2008
Clinical Trial Phase: Phase 3 | Start Date: September 2004
Overall Status: Recruiting
Estimated Enrollment: 600
Brief Summary
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)”
Condition Keyword(s):
Intervention(s):
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.
Study Type: Interventional
Study Design: Treatment, Randomized
Detailed Clinical Trial 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.
Outcome Measures for this Clinical Trial
Primary:
- Conditional event-free survival No
Secondary:
- Overall survival No
- Acute and long-term toxicity Yes
- Non-lymphoma-related deaths and early deaths (excluding deaths occurring after second line treatment for failure or relapse) No
Criteria for Participation in this Clinical Trial
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
Clinical Trials Locations, Contact Details, and Sponsors
Lead Sponsor: Children's Cancer and Leukaemia Group
Kinderklinik
Giessen D-35385 Germany
Our Lady's Hospital for Sick Children Crumlin
Dublin 12 Ireland
Addenbrooke's Hospital
Cambridge England CB2 2QQ United Kingdom
Birmingham Children's Hospital
Birmingham England B4 6NH United Kingdom
Children's Hospital - Sheffield
Sheffield England S10 2TH United Kingdom
Great Ormond Street Hospital for Children
London England WC1N 3JH United Kingdom
Institute of Child Health at University of Bristol
Bristol England BS2 8AE 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
Oxford Radcliffe Hospital
Oxford England 0X3 9DU United Kingdom
Queen's Medical Centre
Nottingham England NG7 2UH United Kingdom
Royal Liverpool Children's Hospital, Alder Hey
Liverpool England L12 2AP United Kingdom
Royal London Hospital
London England E1 1BB United Kingdom
Royal Manchester Children's Hospital
Manchester England M27 4HA United Kingdom
Royal Marsden - Surrey
Sutton England SM2 5PT United Kingdom
Sir James Spence Institute of Child Health
Newcastle-Upon-Tyne England NE1 4LP United Kingdom
Southampton General Hospital
Southampton England SO16 6YD 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
Glasgow Scotland G3 8SJ United Kingdom
Royal Hospital for Sick Children
Edinburgh Scotland EH9 1LF United Kingdom
Childrens Hospital for Wales
Cardiff Wales CF14 4XW United Kingdom
Overall Clinical Trial Officials and Contacts
Robert F. Wynn, MD Study Chair Royal Manchester Children's Hospital
Additional Information
Information obtained from ClinicalTrials.gov on July 23, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00275106
Study ID Number: CDR0000454508
ClinicalTrials.gov Identifier: NCT00275106
Health Authority: Unspecified
Clinical trial summary from the National Cancer Institute's PDQ® database
Clinical Trials Authorship and Review
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.