ÃÛÌÒTV

Trial Name:

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.

Design:

This was a multicenter open label randomized phase II trial.

Enrolled PCNSL patients were 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 was administered every three weeks. The maximum number of chemotherapy induction courses was 4. Patients in SD or better after two courses received two more courses of the same primary chemotherapy regimen. Stem-cells harvest was performed in the three arms after the second course. After 4 courses response assessment was performed.

Patients who did not achieve SD or better after the 4th course, as well as those who experienced progressive disease (PD) at any time and those who did not achieve a sufficient stem cell harvest, received WBRT 36-40 Gy +/- tumor bed boost of 9 Gy. Patients who achieved SD or better after the 4th course were stratified according to objective response to primary chemotherapy (CR vs. PR+SD) and to primaryÌýchemotherapy 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 remained in follow-up. Patients who did not achieve a CR after WBRT were managed according to physician’s preferences. Patients who did not achieve a CR after APBSCT weree referred to WBRT.

Status:

Completed.

Population:

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

Publications:

MATRix induction followed by autologous stem cell transplant or whole-brain irradiation in primary CNS lymphoma. 7-year results of the IELSG32 randomized trial.Ìý

Matrix followed by autologous transplant is associated with excellent survival and neutrotolerability in primary CNS lymphoma: Results of the IELSG-32 trial at a median follow-up of 88 months.Ìý

Andrés J M Ferreri, Kate Cwynarski, et al. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma ÃÛÌÒTV Group-32 phase 2 trial.Ìý

Andrés J M Ferreri, Kate Cwynarski, et al. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma ÃÛÌÒTV Group-32 (IELSG32) phase 2 trial.Ìý

Contact Details:

All Trial enquiries should be addressed to ctu@soton.ac.uk

Funder

This trial was funded by Cancer Research UK (award reference no. C36711/A12115)

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