Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma
Condition: Central Nervous System Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a multicenter open label randomized phase II trial.

      Enrolled Primary Central Nervous System Lymphoma (PCNSL) patients will be stratified
      according to the IELSG score and randomized to receive one of the follows as primary
      chemotherapy:

        -  Arm A: Methotrexate (MTX) + Cytarabine (Ara-C)

        -  Arm B: MTX + Ara-C + rituximab

        -  Arm C: MTX + Ara-C + rituximab + thiotepa.

      Chemotherapy will be administered every three weeks. The maximum number of chemotherapy
      induction courses will be 4. Patients in Stable Disease (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 Whole Brain Radiation Therapy (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 and to primary chemotherapy regimen and randomly
      allocated to receive as consolidation therapy one of the follows:

        -  Arm D: WBRT 36 Gy +/- boost 9 Gy

        -  Arm E: Carmustine (BCNU) + Thiotepa + Autologous Peripheral Blood Stem Cell Transplant
           (APBSCT) Patients in Complete Response (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.
    


Intervention name(s): Methotrexate; Ara-C; Rituximab; Thiotepa; radiotherapy; BCNU; APBSCT
Intervention type(s): Drug; Drug; Drug; Drug; Radiation; Drug; Other
Intervention description(s): Methotrexate 3.5 g/m2 (0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion) on day 1, every 3 weeks for a maximum of 4 courses.; Cytarabine 2 g/m2 (1 hr infusion, twice a day every 12 hours), on d 2 - 3 every 3 weeks for a maximum of 4 courses; Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles; ARM C: Thiotepa 30 mg/m2 (30 min. Infusion) on day 4 every 3 weeks for a maximum of 4 courses ARM E: Thiotepa 5 mg/kg in 250 ml saline sol 2-hr inf. every 12 hrs days -5 & -4; Photons of 4-10 Mev, 180 cGy per day, 5 weekly fractions. Whole-brain will be irradiated by two opposite lateral fields including the first two cervical vertebras and the posterior two thirds of the orbits, which must be shielded after 30 Gy (after 36 Gy in the case of evident intraocular disease at diagnosis). Tumor-bed (boost or partial-brain RT) will be irradiated by 2 to 4 isocentric treatment fields based on tumor location, with all portals treated per each RT session.; BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6; Autologous peripheral blood stem cell transplant (APBSCT)
Other intervention name(s): Cytarabine; MabThera; Carmustine
Intervention MeSH terms: Cytarabine; Rituximab; Methotrexate; Thiotepa; Carmustine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: newly diagnosed primary central nervous system lymphoma