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

This study has been terminated.
(Withdrawn due to an excess of toxic deaths)
Sponsor:
Collaborator:
European Inter-Group Co-operation on Childhood Non-Hodgkin Lymphoma
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00275106
First received: January 10, 2006
Last updated: July 9, 2013
Last verified: April 2008
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: 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
Procedure: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Conditional event-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Acute and long-term toxicity [ Designated as safety issue: Yes ]
  • Non-lymphoma-related deaths and early deaths (excluding deaths occurring after second line treatment for failure or relapse) [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: September 2004
Study Completion Date: August 2012
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
  Hide Detailed Description

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

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00275106

Locations
Germany
Kinderklinik
Giessen, Germany, D-35385
Ireland
Our Lady's Hospital for Sick Children Crumlin
Dublin, Ireland, 12
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B4 6NH
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom, BS2 8AE
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
Great Ormond Street Hospital for Children
London, England, United Kingdom, WC1N 3JH
Royal London Hospital
London, England, United Kingdom, E1 1BB
Royal Manchester Children's Hospital
Manchester, England, United Kingdom, M27 4HA
Sir James Spence Institute of Child Health
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Queen's Medical Centre
Nottingham, England, United Kingdom, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ
Childrens Hospital for Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
European Inter-Group Co-operation on Childhood Non-Hodgkin Lymphoma
Investigators
Study Chair: Robert F. Wynn, MD Royal Manchester Children's Hospital
Investigator: Tim O.B. Eden, MB, BS, FRCPE, FRCP, FRCPCH, F Christie Hospital NHS Foundation Trust
Study Chair: Alfred Reiter, MD Kinderklinik
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00275106     History of Changes
Other Study ID Numbers: CCLG-NHL-2004-08, CDR0000454508, EU-20598, CCLG-EURO-LIB-02, EICNHL-ERURO-LB02, EUDRACT-2004-0011861-17
Study First Received: January 10, 2006
Last Updated: July 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Asparaginase
BB 1101
Cyclophosphamide
Daunorubicin
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents

ClinicalTrials.gov processed this record on October 22, 2014