Chemotherapy Plus Rituximab Combination for Adult Lymphoblastic Leukemia (B-ALL) and Burkitt's Non-Hodgkin Lymphoma

Study Overview
=================
Brief Summary
-----------------
The study was set up to assess the efficacy and tolerability of a chemotherapy-immunotherapy combination programme originally introduced by GMALL (the German cooperative group for adult acute lymphoblastic leukemia)in 2002, to improve remission rate, overall and disease-free survival rates of adult patients with Burkitt's leukemia and lymphoma. The therapy includes a maximum of six chemotherapy courses (two with high doses of methotrexate and cytarabine) plus anti-CD20 antibody (Rituximab, up to 8 total doses), supplemented by local radiation therapy in the case of initial mediastinal or central nervous system (CNS) involvement or a residual tumor after chemotherapy.

Detailed Description
-----------------
Cycle A1: prednisone-cyclophosphamide pre-phase (5 days), Rituximab on day 0, chemotherapy on days 1-5 (dexamethasone, iphosphamide, vincristine, high-dose methotrexate, triple intrathecal therapy). Cycle B1: Rituximab on day 0, chemotherapy on days 1-5 (dexamethasone, vincristine, cyclophosphamide, high-dose methotrexate, adriamycin, triple intrathecal therapy) Cycle C1: Rituximab on day 0, chemotherapy on days 1-5 (dexamethasone, vindesine, high-dose methotrexate, etoposide, high-dose cytarabine). Cycle A2: like cycle A1, without pre-phase. Cycle B2: like cycle B1. Cycle C2: like cycle C1. Cycle C2 is followed by two additional Rituximab injections. Notes: patients with stage I-II disease without mediastinal tumor or extranodal involvement receive only the first 4 cycles (A1 to A2). patients aged >55 years do not receive cycles C (sequence: A1, B1, A2, B2, A3, B3 or A1, B1, A2, B2 if limited stage, with reduced-dose methotrexate).

Official Title
-----------------
Multicentre Study to Optimize Therapy of Burkitt's Leukemia (B-ALL) and Non-Hodgkin Lymphoma

Conditions
-----------------
Burkitt Lymphoma, B-ALL

Intervention / Treatment
-----------------
* Drug: Chemotherapy-Rituximab combination


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Burkitt's leukemia or lymphoma (new diagnosis) Written informed consent Age > 15 years Exclusion Criteria: pre-treated Burkitt's leukemia or lymphoma psychiatric disorders active second malignancy pregnancy absence of patient's written informed consent participation in other studies that interfere with the study therapy

Ages Eligible for Study
-----------------
Minimum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Chemotherapy-Rituximab combination|Short cycles of high-dose and conventional chemotherapy in combination with rituximab, followed by local radiotherapy in the case of initial mediastinal or central nervous system (CNS) involvement or a residual tumor after chemotherapy. Used drugs are rituximab,cyclophosphamide, prednisone, dexamethasone, vincristine, methotrexate, iphosphamide, teniposide, etoposide, dexamethasone, cytarabine,adriamycin, vincristine, vindesine.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Percentage of patients alive without disease at 5 years from date of diagnosis | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Percentage of patients alive without disease at 5 years from date of remission | 5 years | 
| Cumulative incidence of relapse | Percentage of relapsed patients at 5 years from date of remission | 5 years | 
| Complete remission rate | Percentage of patients achieving complete remission after the first two treatment cycles (defining the early response rate), and then confirmed to remain in complete remission at end of the six chemotherapy blocks. Re-staging procedures include physical examination, blood counts and biochemistry, bone marrow examination , and instrumental tests as appropriate (ultrasound scans, computed tomography, nuclear magnetic resonance, positron emission tomography)depending on clinical presentation of individual subjects. | Up to 24 weeks | 
| Toxicity | Percentage of patients who develop early and late therapy-related toxic side effects (including death in complete remision). Toxicity is defined according to the Common Toxicity Criteria scale (NCI), graded I-IV and referring to both hematological and extrahematologic toxicity. Early toxicity is registered during the first two chemotherapy cycles, and late toxicity following completion of therapy and up to 1 year from diagnosis. | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Burkitt Lymphoma, B-ALL, Adult patients