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The University of Southampton
Southampton Clinical Trials Unit

IELSG 32

Title

IELSG 32 - Randomized phase II trial on primary chemotherapy with high-dose methotrexate and high-dose cytarabine with or without thiotepa, and with or without rituximab, followed by brain irradiation vs. high-dose chemotherapy supported by autologous stem cells transplantation for immunocompetent patients with newly diagnosed primary cns lymphoma 

Description

A randomised Phase II Trial on primary chemotherapy with high-dose Methotrexate (MTX) and high-dose Cytarabine (Ara-C), with or without Thiotepa, and with or without Rituximab. This is followed by brain irradiation vs. high-dose chemotherapy supported by autologous stem cell transplantation for immunocompetent patients with newly diagnosed primary CNS lymphoma (PCNSL). 

Objectives

To determine, at first randomisation, the activity of three different chemotherapy combinations with high-dose Methotrexate (HD-MTX) + high-dose Cytarabine (HD-araC), HD-MTX + HD-araC + Rituximab and HD-MTX + HD-araC + Rituximab + Thiotepa in patients with newly diagnosed PCNSL.

To determine, at second randomisation, the efficacy of two consolidation strategies: conventional whole-brain radiotherapy (WBRT) vs. highdose chemotherapy supported by autologous stem cell transplantation (HDC + ASCT) in patients with newly diagnosed PCNSL.

Trial Design

This is a multicenter open label randomized phase II trial.


Enrolled PCNSL patients will be stratified according to the IELSG score and randomized to receive MTX + Ara-C (Arm A) or MTX + Ara-C + rituximab (Arm B) or MTX + Ara-C + rituximab + thiotepa (Arm C) as primary chemotherapy. Chemotherapy will be administered every three weeks. The maximum number of chemotherapy induction courses will be 4. Patients in SD or better after two courses will receive two more courses of the same primary chemotherapy regimen. Stem-cells harvest will be performed in the three arms after the second course. After 4 courses response assessment will be performed.


Patients who will not achieve SD or better after the 4th course, as well as those who will experience progressive disease (PD) at any time and those who will not achieve a sufficient stem cell harvest, will receive WBRT 36-40 Gy +/- tumor bed boost of 9 Gy. Patients who will achieve SD or better after the 4th course will be stratified according to objective response to primary chemotherapy (CR vs. PR+SD) and to primary chemotherapy regimen (A vs. B vs. C) and randomly allocated to receive WBRT 36 Gy +/- boost 9 Gy (Arm D) or BCNU + Thiotepa + APBSCT (Arm E) as a consolidation therapy. Patients in CR after WBRT or APBSCT will remain in follow-up. Patients who will not achieve a CR after WBRT will be managed according to physician’s preferences. Patients who will not achieve a CR after APBSCT will be referred to WBRT.


At the end of the study a Monitoring Committee will review the data concerning the CR rate and the safety profile and will take the decision whether to continue with a phase III trial. In this case, the patients enrolled in the phase II study will be included in the phase III analysis.

Trial Status

Closed to Recruitment - in follow-up 

Population

126 immunocompetent patients with newly diagnosed PCNSL of any histological category eligible for high-dose chemotherapy supported by autologous stem cell transplantion. 

Consideration

Patients will be centrally registered and simultaneously randomised at the IELSG Coordination and Data Management Office in Switzerland after the verification of the inclusion criteria and prior to the start of treatment.

Trial Team:

Senior Trial Manager:

Kelly Cozens (023 8120 8834)

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