Short Term Intensified Chemo-immunotherapy in HIV-positive Patients With Burkitt Lymphoma

The activity of feasibility of the proposed program will be assessed in HIV+ patients with Burkitt lymphoma with the aim to improve tolerability, minimize source consuming and supporting treatment and redu ce late sequels. Available combinations in this setting are really source demanding and toxic combinations showing high rates of septic complication and a treatment-related mortality of near 20%.

• Induction Phase (Drug), also known as Short-term intensive sequential chemoimmunotherapy: * dd -2 to 1: Methylprednisolone * dd 0-1, Cyclophosphamide, associated on day 0 with Vincristine * dd 2, Rituximab * dd 7, Methotrexate * dd 14, Rituximab * dd 15, Etoposide * dd 21, Methotrexate * dd 29, Rituximab and Doxorubicin * dd 36, Rituximab and VCR At the end of this induction phase, subsequent treatment will be performed according to the objective response: 1. pts in CR: consolidation phase followed by bulky site irradiation 2. pts in PR: consolidation phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation 3. pts with SD after induction or PD during or after induction: intensification phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation
• Consolidation Phase (on day +50) (Drug), also known as high-dose cytarabine; consolidation phase: * dd 1-2: cytarabine twice a day * dd 3 and 11: rituximab * dd 11-13: leukapheresis for PBPC collection.
• Intensification phase (Drug), also known as unresponsive patients, refractory disease: 1. One or two courses of R-IVAC or R-ICE chemoimmunotherapy regimen, every three weeks as debulking. 2. CTX (dd 1) associated with rituximab on dd 3 and 10, followed by PBPC collection (dd 11-13); 3. AraC every 12 hours for four days (dd -5 to -2) supported by reinfusion of CD34+ cells (dd 0), rituximab infusion (dd -1 and +11) and second in-vivo purged PBPC collection (if needed).
• BEAM conditioning (Drug), also known as Conditioning regimen, autologous transplantation: BCNU on dd 1; VP-16 every 12 hours on dd 2-5 and araC every 12 hours on dd 2-5; melphalan on dd 6, followed by the reinfusion of CD34+ cells
• Consolidation radiotherapy (Radiation), also known as bulky irradiation; residual lesion: At the end of the whole program, patients will be evaluated for involved-field irradiation with 6-10 MeV photons and a dose of 36 Gy (2 Gy/d, five fractions a week). Three subgroups of patients will be considered for radiotherapy

Primary outcomes

• evaluation of activity of the induction phase in terms of complete remission rate [at the end of the induction phase of the investigational intensive chemotherapy, an expected average of 45 days]: Objective lymphoma response achieved after the induction phase of the experimental treatment.

Secondary outcomes

• Feasibility and tolerability of the investigational intensive chemotherapy in terms of grade ≥4 adverse events [participants will be followed for the duration of the whole experimental program, an expected average of 100 days]: Assessment of incidence of grade 4 AE during experimental treatment (induction, consolidation and intensification phases as well as conditioning and autologous stem cell transplantation (if indicated)
• Feasibility and tolerability of the consolidation phase followed by BEAM conditioning and autologous stem cell transplantation in terms of prevalence of grade ≥4 adverse events [participants will be followed for the duration of the whole experimental program, an expected average of 100 days]
• Feasibility and tolerability of intensification phase in terms of prevalence of grade ≥4 adverse events [participants will be followed for the duration of the whole experimental program, an expected average of 100 days]: Participants who will not achieve a complete or partial response after induction and consolidation phases will be referred to intensification phase, which will be followed by BEAM + ASCT. These patients will be assess for tolerabbility and AE during these therapeutic phases.
• Activity of the whole investigational program in terms of complete remission rate [at the end of the whole program, an expected average of 100 days]: Participants will be assessed by conventional exams to define complete remission rate after the whole experiemntal program; that is after consolidation phase for patients who achieved complete remission after induction phase, after BEAM + ASCt for patients who achieved partial response after induction phase, and after intensification phase for patients who did not achieve an objective response after induction phase.

Sex: All, ages: 18 Years to 60 Years

Inclusion Criteria:

* Histologic diagnosis of Burkitt's lymphoma (WHO 2008)
* HIV sero-positivity
* Age ≥18 and ≤60 years
* ECOG-PS ≤3

Exclusion Criteria:

* CNS parenchymal involvement
* Absolute neutrophil count <1.000 cells/μL and platelets count <75 × 109/L (Burkitt unrelated)
* Creatinine >1,5N (Burkitt unrelated)
* SGOT and/or SGTP >2,5N (Burkitt unrelated)
* Bilirubin >2N (Burkitt unrelated)
* Severe psychiatric illness or any other clinical, social or psychological condition that could interfere with patient's adherence and compliance
* Significant cardiac disease or acute myocardial infarction in the last 12 months
* Severe active infection (except for HBV and/or HCV co-infection)

• Andrés JM Ferreri, MD, Study chair, San Raffaele Scientific Institute, Milano, Italy