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)”

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

Study Primary Completion Date: December 2009

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.

Intervention(s) in this Clinical Trial

• 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

Primary Measures

• Conditional event-free survival
  • Safety Issue?: No

Secondary Measures

• Overall survival
  • Safety Issue?: No
• Acute and long-term toxicity
  • Safety Issue?: Yes
• Non-lymphoma-related deaths and early deaths (excluding deaths occurring after second line treatment for failure or relapse)
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 21 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Children's Cancer and Leukaemia Group

Overall Clinical Trial Officials and Contacts

Robert F. Wynn, MD Study Chair Royal Manchester Children's Hospital  

Information obtained from ClinicalTrials.gov on July 02, 2009

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