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

• ClinicalTrials.gov Identifier: NCT01599559
• Recruitment Status: Active, not recruiting
• First Posted: May 16, 2012
• Last Update Posted: January 22, 2021
• Sponsor: International Extranodal Lymphoma Study Group (IELSG)
• Information provided by (Responsible Party): International Extranodal Lymphoma Study Group (IELSG)

Tracking Information

• First Submitted Date: May 10, 2012
• First Posted Date: May 16, 2012
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: October 2012
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 15, 2012)

Progression free survival (PFS) [ Time Frame: 2 years from the randomization ]

The primary outcome endpoint will be Progression Free Survival (PFS) in patients PET-negative after R-chemotherapy. Failure events for PFS are progression (defined as an increase in size of existing masses or the development of new sites of disease using the same radiological investigations CT or PET/CT and/or MRI - as for the pre-chemotherapy assessment) or death from any cause.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: May 15, 2012): Overall survival (OS) [ Time Frame: 5 years from registration ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: IELSG37: A Randomized, Open-label, Multicentre, Two-arm 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 (PMLBCL)

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Primary Mediastinal B-cell Lymphoma

Intervention

• Other: observation
  observation
• Radiation: 3D-Conformal Radiotherapy (3D-CRT)
  Radiation treatment should start within 6-8 weeks after the end of chemotherapy.

Study Arms

• Experimental: observation
  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.
  Intervention: Other: observation
• Active Comparator: mediastinal irradiation
  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.
  Intervention: Radiation: 3D-Conformal Radiotherapy (3D-CRT)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 26, 2016): 540
• Original Estimated Enrollment (submitted: May 15, 2012): 752
• Estimated Study Completion Date: May 2025
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, Argentina, Canada, China, Czechia, Germany, Norway, Poland, Portugal, Sweden, Switzerland, Ukraine, United Kingdom, United States
• Removed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT01599559
• Other Study ID Numbers: IELSG37
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: International Extranodal Lymphoma Study Group (IELSG)
• Study Sponsor: International Extranodal Lymphoma Study Group (IELSG)
• Collaborators: Not Provided

Investigators

• Study Chair: Maurizio Martelli, MD; Università La Sapienza (Rome - Italy)
• Study Chair: Andrew J Davies, MD; University of Southampton (UK)
• Study Chair: Mary Gospodarowicz, MD; Princess Margaret Hospital Toronto (Canada)
• Study Chair: Sally F Barrington, MD; St. Thomas' - London (UK)
• Study Chair: Alberto Biggi, MD; AO S. Croce e Carle, Cuneo (Italia)
• Study Chair: Annibale Versari, MD; S.Maria Nuova Hospital, Reggio Emilia (Italia)
• Study Chair: Gianni Ciccone, MD; CPO Torino (Italy)
• Study Chair: Stèphane Chauvie, MD; AO S. Crtoce e Carle - Cuneo (Italy)
• Study Chair: Luca Ceriani, MD; IOSI - Bellinzona (Switzerland)

• PRS Account: International Extranodal Lymphoma Study Group (IELSG)
• Verification Date: January 2021