Clinical trial NCT00275106: Prednisolone or Dexamethasone Combined With Chemotherapy in Treating Young Patients With Newly Diagnosed Lymphoblastic Lymphoma
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lymphoma
Keywords: stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: European Inter-group Cooperation on Childhood and Adolescent Non Hodgkin Lymphoma
First posted: 2006-01-11
Enrollment: 600
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Conditional event-free survival
Secondary outcomes:
measure: Overall survival
measure: Acute and long-term toxicity
measure: Non-lymphoma-related deaths and early deaths (excluding deaths occurring after second line treatment for failure or relapse)
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: Kinderklinik
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children Crumlin
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Bristol
country: United Kingdom
facility: Institute of Child Health at University of Bristol
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: Royal London Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Cardiff
country: United Kingdom
facility: Childrens Hospital for Wales
state: Wales
Study officials:
affiliation: Royal Manchester Children's Hospital
name: Robert F. Wynn, MD
role: STUDY_CHAIR
affiliation: The Christie NHS Foundation Trust
name: Tim O.B. Eden, MB, BS, FRCPE, FRCP, FRCPCH, F
affiliation: University Hospital Erlangen
name: Alfred Reiter, MD
role: STUDY_CHAIR
References:
citation: Landmann E, Burkhardt B, Zimmermann M, Meyer U, Woessmann W, Klapper W, Wrobel G, Rosolen A, Pillon M, Escherich G, Attarbaschi A, Beishuizen A, Mellgren K, Wynn R, Ratei R, Plesa A, Schrappe M, Reiter A, Bergeron C, Patte C, Bertrand Y. Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma. Haematologica. 2017 Dec;102(12):2086-2096. doi: 10.3324/haematol.2015.139162. Epub 2017 Oct 5.