Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active Under 22 Other CCLG-NHL-2004-08 EU-20598, CCLG-EURO-LIB-02, NCT00275106, EICNHL-ERURO-LB02, EUDRACT-2004-0011861-17

Objectives

Primary

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

Secondary

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

Entry 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

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

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

Expected Enrollment

Approximately 600 patients will be accrued for this study.

Outcomes

Conditional event-free survival

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)

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.

Trial Contact Information

Trial Lead Organizations

Children's Cancer and Leukaemia Group

Robert Wynn, MD, Protocol chair		Ph: 44-161-922-2172 Email: robert.wynn@cmmc.nhs.uk
Tim Eden, MB, BS, FRCPE, FRCP, FRCPCH, FRCPath, Protocol co-chair		Ph: 44-161-446-3094 Email: tim.eden@manchester.ac.uk

European Inter-Group Co-operation on Childhood Non-Hodgkin Lymphoma

Alfred Reiter, MD, Protocol chair		Ph: 49-641-994-3420

Germany
	Giessen
	Kinderklinik
		Alfred Reiter, MD	Ph:  49-641-994-3420
Ireland
	Dublin
	Our Lady's Hospital for Sick Children Crumlin
		Fin Breatnach, MD, FRCPE	Ph:  353-1-409-6659
			Email: fin.breatnach@olhsc.ie
United Kingdom
England
	Birmingham
	Birmingham Children's Hospital
		Martin English, MD	Ph:  44-121-333-8412
			Email: martin.english@bch.nhs.uk
	Bristol
	Institute of Child Health at University of Bristol
		Pamela Kearns, MD	Ph:  44-117-342-0205
	Cambridge
	Addenbrooke's Hospital
		Amos Burke, MD	Ph:  44-1223-348-151
	Leeds
	Leeds Cancer Centre at St. James's University Hospital
		Adam Glaser, MD	Ph:  44-113-206-4984
			Email: adam.glaser@leedsth.nhs.uk
	Leicester
	Leicester Royal Infirmary
		Mabrouk Madi, MD	Ph:  44-116-258-5959
	Liverpool
	Royal Liverpool Children's Hospital, Alder Hey
		Heather McDowell, MD	Ph:  44-151-293-3679
	London
	Great Ormond Street Hospital for Children
		Gill Levitt, MD	Ph:  44-20-7405-9200 ext. 0073
	Royal London Hospital
		Ananth Shankar, MD	Ph:  44-20-7380-9950
			Email: a.shankar@cancer.org.uk
	Manchester
	Royal Manchester Children's Hospital
		Bernadette Brennan, MD	Ph:  44-161-922-2227
			Email: bernadette.brennan@cmmc.nhs.uk
	Newcastle-Upon-Tyne
	Sir James Spence Institute of Child Health
		Juliet Hale, MD	Ph:  44-191-282-4101
			Email: j.p.hale@ncl.ac.uk
	Nottingham
	Queen's Medical Centre
		Martin Hewitt, MD, BSc, FRCP, FRCPCH	Ph:  44-115-924-9924 ext. 63394
			Email: martin.hewitt@nuh.nhs.uk
	Oxford
	Oxford Radcliffe Hospital
		Kate Wheeler, MD	Ph:  44-186-522-1066
	Sheffield
	Children's Hospital - Sheffield
		Mary Gerrard, BSc, MBChB, FRCP, FRCPCH	Ph:  44-114-271-7366
			Email: mary.gerrard@sch.nhs.uk
	Southampton
	Southampton General Hospital
		Janice Kohler, MD, FRCP	Ph:  44-23-8079-6942
	Sutton
	Royal Marsden - Surrey
		Mary Taj, MD	Ph:  44-20-8642-6011 ext. 3089
Northern Ireland
	Belfast
	Royal Belfast Hospital for Sick Children
		Anthony McCarthy, MD	Ph:  44-289-063-3631
			Email: anthonymcarthy@royalhospital.n.i.nhs.uk
Scotland
	Aberdeen
	Royal Aberdeen Children's Hospital
		Derek King, MD	Ph:  44-1224-681-818
	Edinburgh
	Royal Hospital for Sick Children
		W. Hamish Wallace, MD	Ph:  44-131-536-0426
	Glasgow
	Royal Hospital for Sick Children
		Milind Ronghe, MD	Ph:  44-141-201-9309
Wales
	Cardiff
	Childrens Hospital for Wales
		Heidi Traunecker, MD, PhD	Ph:  44-29-2074-2285
			Email: heidi.traunecker@cardiffandvale.wales.nhs.uk

Registry Information
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)
Trial Start Date		2004-09-01
Trial Completion Date		2009-12-01 (estimated)
Registered in ClinicalTrials.gov		NCT00275106
Date Submitted to PDQ		2005-09-15
Information Last Verified		2008-04-27

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