NCT02531841

High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma

High-dose Chemotherapy and Autologous Stem Cell Transplant or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma - Randomized Phase III Trial

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 250 (estimated)
• Sponsor: University Hospital Freiburg · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

In the presently planned multicentre Phase III trial the two therapies will be compared: Patients will be randomized after intensified induction treatment with 4 cycles rituximab, methotrexate, cytarabine and thiotepa (MATRix) between first-line high-dose chemotherapy against conventional consolidating therapy with 2 cycles of conventional chemotherapy with R-DeVIC (rituximab, dexamethasone, etoposide, ifosfamide, carboplatin).

Detailed description

Trial purpose and rationale Primary central nervous system lymphoma (PCNSL) is a highly aggressive disease with rising incidence over the past 30 years. Similar to other hematological diseases, the rationale for consolidation in PCNSL is the elimination of minimal residual disease. The efficacy of WBRT, which is the current standard for consolidation after HD-MTX-based systemic treatment, is being compared to HDT-ASCT in the ongoing IELSG-32 trial. High-dose chemotherapy with carmustine or busulfan and thiotepa followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed eligible patients, but also in the salvage situation. The question we aim to answer is whether HDT-ASCT is superior to conventional therapy as consolidation after intensified immunochemotherapy in newly diagnosed PCNSL. Rationale for this study: Based on previously obtained good results from the treatment of recurrent or refractory PCNSL the DeVIC protocol was chosen for conventional consolidation treatment. This protocol, originally designed as a salvage protocol for aggressive NHL, crosses the blood-brain barrier and consists of multidrug resistant unrelated agents. Treatment plan and procedure Interventions Induction treatment 4 cycles (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d 0,5) * Methotrexate 3,5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Patients with PD after two cycles, SD/PD after four cycles of induction therapy or insufficient stem-cell harvest after three cycles are ineligible for randomization. Consolidation Arm A 2 cycles of R-DeVIC (every 3 weeks): * Rituximab 375 mg/m²/d i.v. (d0) * Dexamethasone 40 mg/d i.v. (d1-3) * Etoposide 100 mg/m²/d i.v. (d1-3) * Ifosfamide 1500 mg/m²/d i.v. (d1-3) * Carboplatin 300 mg/m² i.v. (d1) Consolidation Arm B High-dose chemotherapy (HDT-ASCT): * Carmustine\* 400 mg/m² i.v. (d-6) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) \* if carmustine is not available at the investigation site, busulfan can be administered instead: * Busulfan 3,2 mg/kg/d (d-8-(-7)) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0)

Conditions

• Diffuse Large B-cell-lymphoma

Interventions

Type	Name	Description
DRUG	Arm A (Fortecortin®-ETOPOPHOS®-IFO-cell®-CARBO-cell®)	Arm A 4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation 2 cycles of R-DeVIC (every 3 weeks): * Rituximab 375 mg/m²/d i.v. (d0) * Dexamethasone 40 mg/d i.v. (d1-3) * Etoposide 100 mg/m²/d i.v. (d1-3) * Ifosfamide 1500 mg/m²/d i.v. (d1-3) * Carboplatin 300 mg/m² i.v. (d1)
DRUG	Arm B (TEPADINA®-CARMUBRIS®-Busilvex®)	4 cycles MATRix (every 3 weeks), stem-cell harvest after 2nd cycle: * Rituximab 375 mg/m²/d i.v. (d0,5) * Methotrexate 3.5 g/m² i.v. (d1) * Cytarabine 2 x 2 g/m²/d i.v. (d2-3) * Thiotepa 30 mg/m² i.v. (d4) Consolidation High-dose chemotherapy (HDT-ASCT): * Carmustine\* 400 mg/m² i.v. (d-6) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0) \* if carmustine is not available at the investigation site, busulfan can be administered instead: * Busulfan 3,2 mg/kg/d (d-8-(-7)) * Thiotepa 2 x 5 mg/kg/d i.v. (d-5-(-4)) * Autologous Stem Cell Transplantation (d0)

Timeline

• Start date: 2014-07-01
• Primary completion: 2017-11-01
• Completion: 2019-12-01
• First posted: 2015-08-25
• Last updated: 2015-08-25

Locations

2 sites across 1 country: Germany