Clinical Trial: Risk-stratified Sequential Treatment of Post-transplant Lymphoproliferative Disease (PTLD) With Rituximab SC and Immunochemotherapy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Risk-stratified Sequential Treatment of Post-transplant Lymphoproliferative Disease (PTLD) With 4 Courses of Rituximab SC Followed by 4 Courses of Rituximab SC, 4 Courses

Brief Summary:

Post-transplant lymphoproliferative disorders (PTLD) differ clinically from lymphoma in the general (immunocompetent) population due to their higher incidence and their frequent association with Epstein-Barr virus. Previous clinical trials have shown their remarkably good response to rituximab as well as to chemotherapy.

The PTLD-1 trial demonstrated the efficacy and safety of sequential immunochemotherapy with 4 courses of rituximab IV followed by 4 cycles of CHOP chemotherapy. Compared to trials of rituximab monotherapy in PTLD, median overall survival was extended from 2.4 to 6.5 years. Compared to previous trials of chemotherapy, complications were reduced. In addition, we noted that those patients who already had a good response to the first four cycles of rituximab did better overall than those who did not. As a consequence, the PTLD-1/3 trial introduced risk-stratification in sequential treatment according to the response to the first 4 courses of rituximab monotherapy. Those patients with a complete remission went on to receive four further courses of rituximab whereas those who did not received rituximab and CHOP chemotherapy. Interim results have demonstrated that it is safe to restrict chemotherapy treatment in this manner and thus established the concept of treatment stratification based on the response to rituximab.

The PTLD-2 trial is the next step in the development of this strategy. Compared to the PTLD-1/3 trial, the key difference is the use of subcutaneous instead of intravenous rituximab application. Interim results from an ongoing trial of patients with follicular lymphoma (NCT01200758) have shown that subcutaneous administration results in increased blood levels and in non-inferior remission rates. Furthermore, the stratification strategy is refined based on observations from the previous PTLD-1 and P

Detailed Summary:
Sponsor: Diako Ev. Diakonie-Krankenhaus gemeinnützige GmbH

Current Primary Outcome: Event free survival (EFS) of low-risk patients in the intention to treat population with following definitions for low-risk and event: [ Time Frame: two years ]

Time from start of treatment to event with following definitions for low-risk and event:

  1. Low-risk:

    • all patients in complete remission at interim staging, i.e. 4 weeks after the four weekly courses of rituximab SC monotherapy
    • all patients in partial remission at interim staging with an initial international prognostic index (IPI) of 0,1 or 2

  2. Events:

    • any grade III or IV infection during the treatment period
    • treatment discontinuation from any reason
    • disease progression at any time
    • death from any reason


Original Primary Outcome: Event free survival (EFS) of low-risk patients in the intention to treat population with following definitions for low-risk and event: [ Time Frame: two years ]

Time from start of treatment to event with following definitions for low-risk and event:

  1. Low-risk:

    • all patients in complete remission at interim staging, i.e. 4 weeks after the four weekly courses of rituximab SC monotherapy
    • all patients in partial remission at interim staging with an initial international prognostic index (IPI) of 0,1 or 2
    • all patients in partial remission at interim staging with an negative PET scan*

  2. Events:

    • any grade III or IV infection during the treatment period
    • treatment discontinuation from any reason
    • disease progression at any time
    • death from any reason


Current Secondary Outcome:

  • Overall survival [ Time Frame: Two years ]
  • Time to progression [ Time Frame: two years ]
  • Progression-free survival [ Time Frame: two years ]
  • Response at interim staging [ Time Frame: day 50 ]
  • Response after full treatment [ Time Frame: three months ]
  • Duration of response [ Time Frame: two years ]
  • Treatment-related mortality [ Time Frame: three months ]


Original Secondary Outcome: Same as current

Information By: Diako Ev. Diakonie-Krankenhaus gemeinnützige GmbH

Dates:
Date Received: January 20, 2014
Date Started: February 3, 2015
Date Completion: September 2019
Last Updated: February 26, 2017
Last Verified: February 2017