Intergroup Trial for Children or Adolescents With Primary Mediastinal Large B-Cell Lymphoma: DA-EPOCH-Rituximab Evaluation

Study Overview
=================
Brief Summary
-----------------
Phase II trial to determine the efficacy of Dose Adjusted-EPOCH-Rituximab regimen in children and adolescent with primary mediastinal large B cell lymphoma in terms of event free survival.

Official Title
-----------------
Intergroup Trial for Children or Adolescents With B-Cell NHL or B-AL: Evaluation of Rituximab Efficacy and Safety in High Risk Patients - Phase II Trial of DA-EPOCH-Rituximab in PMLBL

Conditions
-----------------
Primary Mediastinal Large B Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, Rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven Primary Mediastinal Large B-Cell Lymphoma (PMLBL). PMLBL without central nervous system (CNS) involvement. 6 months to less than 18 years of age at the time of consent. Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: during twelve months for women, taking into account the characteristics of rituximab Complete initial work-up within 8 days prior to treatment that allows definite staging. Able to comply with scheduled follow-up and with management of toxicity. Signed informed consent from patients and/or their parents or legal guardians Exclusion Criteria: Follicular lymphoma, mucosa-associated lymphoid tissue (MALT) and nodular marginal zone PMLBL patients with CNS involvement Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology. Evidence of pregnancy or lactation period. There will be no exclusion criteria based on organ function. Past or current anti-cancer treatment except corticosteroids during less than one week. Tumor cell negative for CD20 Prior exposure to rituximab. Severe active viral infection, especially hepatitis B. Hepatitis B carrier status history of hepatitis B virus (HBV) or positive serology. Participation in another investigational drug clinical trial. Patients who, for any reason, are not able to comply with the national legislation.

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 17 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DA-EPOCH-R<br>6 courses of Dose Adjusted-EPOCH-Rituximab | Drug: Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, Rituximab<br>* 6 courses of Dose Adjusted-EPOCH-Rituximab Rituximab 375 mg/m² i.v.: one injection at each of the 6 courses of EPOCH.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival | Minimum time to death from any cause, presence of viable cells in residue after 6th DA-EPOCH course, relapse, progressive disease, or second malignancy measured from registration. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Overall survival | 5 years | 
| Acute toxicity | Acute toxicity during treatment according to NCI-CTC V4 | 6 months | 
| Long term toxicity | Long term toxicity, especially immune reconstitution, cardiac toxicity | 5 years |