Randomized, Open-label, Two-arms, Phase III Comparative Study Assessing the Role of Involved Mediastinal Radiotherapy After Rituximab Containing Chemotherapy Regimens to Patients With Newly Diagnosed Primary Mediastinal Large B-Cell Lymphoma

International Extranodal Lymphoma Study Group (IELSG)

Status: Active, not recruiting

Conditions: Primary Mediastinal B-cell Lymphoma

Treatments: Radiation: 3D-Conformal Radiotherapy (3D-CRT); Other: observation

Study type: Interventional

Funder types: Other

Identifiers

NCT01599559

IELSG37

Details and patient eligibility

About

Primary mediastinal large B cell lymphoma is treated with a combination of chemotherapy and the monoclonal antibody rituximab (chemoimmunotherapy).

Following chemoimmunotherapy patients receive radiation therapy if they have residues which may be active tumour. However at the end of chemoimmunotherapy the majority of patients show tissue scarring that is not necessarily active tumor. In recent years, PET/CT has proved to be a good tool to accurately identify active tumor from scar tissue in patients treated for mediastinal lymphoma.The purpose of this trial is to test whether radiation therapy is really necessary in patients where PET/CT has shown that the tumor is no longer active. Therefore we will compare radiation treatment with careful observation.

Patients that at the end of conventional treatment of chemoimmunotherapy have a negative PET/CT (i.e., without residues suspected to contain active tumor), will randomly assigned to two different treatment groups: one treatment group will receive the radiation treatment, and the other treatment group will receive careful observation.

The trial is planned according to a non-inferiority design aimed at demonstrating that progression free survival after the experimental treatment (observation) is not worse than after the standard comparator (mediastinal irradiation.Participation in this study could spare patients with complete remission at the end of chemo immunotherapy (PET/CT negative) radiation therapy that may be unnecessary.

Enrollment: 540 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Previously untreated primary mediastinal diffuse large B-cell lymphoma, CD20 positive.
• Patients must have histological confirmation of the diagnosis (it is recommended that the immunohistochemical panel includes: CD45, CD20, CD30, CD15, CD10, BCL6, BCL2, MUM-1), and in addition have a dominant mass within the anterior mediastinum.
• No evidence of extranodal disease outside the chest including spleen and bone marrow.
• Age at least 18 years.
• Fit to receive chemotherapy and radiotherapy with curative intent.
• Patients will be eligible if the treatment phase consisting in a Rituximab combined with any anthracycline-containing chemotherapy regimen without consolidation with autologous stem cell support (e.g., 6 cycles of CHOP14-21, DA-EPOCH, Mega-CHOP or 12 weeks of VACOP-B or MACOP-B).
• At least 6 courses of Rituximab should be administered
• Able and willing to give informed consent, and to undergo staging including PET scanning
• Willingness to comply with an appropriate contraceptive method in women of childbearing potential or men.
• Histological diagnostic material available for review.

Exclusion criteria

• History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 5 years.
• Evidence of clinically significant cardiac disease at diagnosis, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry. Cardiac impairment due to local extension of lymphoma will not be an exclusion criterion in the absence of other cardiac disease.
• Known HIV-positive serology.
• Pregnant or lactating women.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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540 participants in 2 patient groups

observation

Experimental group

Description:

Follow up visits are scheduled from randomization. Patients will be seen at 3-months intervals for 24 months, then every 6 months until 5 years from randomization.

Treatment:

Other: observation

mediastinal irradiation

Active Comparator group

Description:

Radiotherapy will be delivered in this phase III protocol, as alternative to observation, as consolidation treatment in patients achieving a CR status (PET/CT scan negative) at the end of R-chemotherapy, with a total dose of 30 Gy.

Treatment:

Radiation: 3D-Conformal Radiotherapy (3D-CRT)