Clinical Trial: Obinutuzumab Containing Conditioning Regimen for Patients With Poor Risk CLL or Richter`s Transformation Requiring Allogeneic Stem Cell Transplantation

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Obinutuzumab Containing Conditioning Regimen for CLL Patients and Patients With Richter`s Transformation Requiring an Allogeneic Stem Cell Transplantation

Brief Summary: The primary objective of the study is to evaluate the feasibility, efficacy and safety of an obinutuzumab containing conditioning regimen for poor risk CLL patients and patients with Richter`s transformation requiring an allogeneic stem cell transplantation.

Detailed Summary: CLL is the most common haematological malignancy in the western world. Though in the majority it behaves like a chronic disease with minimal impact on life expectancy, in around 15-20% of the patients it takes a very aggressive course. Patients who experience a high grade transformation, i.e., Richter`s transformation also have a poor prognosis. Despite the advent of new therapeutic agents like Bcl-2 and BTK inhibitors which are revolutionising the outlook for this particular patient cohort, allogeneic stem cell transplantation is the only currently available therapy with the potential to cure. The non relapse mortality associated with this treatment is a major deterrent for physicians and patients alike to opt this intervention. We propose a trial to study the use of a B-cell depleting agent, obinutuzumab to simultaneously reduce tumour bulk control and offer GvHD prophylaxis in the peri-transplant setting and thereby analyse its impact on non relapse morbidity and mortality as well as maximum minimum residual disease (MRD) eradication. All patients with poor risk CLL (current EBMT criteria) and Richter`s transformation with the best possible response to available therapies will be considered for the trial. Due to the poor disease control associated with peri-transplant T-cell depletion, obinutuzumab will be used instead of T-cell depleting agents as GvHD prophylaxis.
Sponsor: German CLL Study Group

Current Primary Outcome: PD-free rate [ Time Frame: 12 months post-transplant ]

Rate of patients free from disease progression (key efficacy endpoint)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Minimal residual disease (MRD) negativity rate [ Time Frame: days +60, +90, +180, +270 and months 12, 18 and 24 post-transplant ]
    Minimal residual disease negativity rate at different time points
  • Overall response rate (ORR) [ Time Frame: 6 months post-transplant ]
    The overall response rate (ORR) is defined as the proportion of patients having achieved a CR/CRi, clinical CR/CRi or PR (including PR with lymphocytosis) as best response (according to the IWCLL guidelines (2008)) until and including the response assessment six months after transplantation (=number of patients with best response CR/CRi, clinical CR/CRi or PR (with or without lymphocytosis) divided by the number of the ITT population)
  • Progression-free survival (PFS) [ Time Frame: up to month 24 post-transplant ]
    Time from the date of enrolment to the date of first occurrence of progression (determined using standard IWCLL guidelines) or death from any cause, whichever occurs first.
  • Event-free survival (EFS) [ Time Frame: up to month 24 post-transplant ]
    Time from the date of enrolment to the date of first occurrence of progression (determined using standard IWCLL guidelines), death from any cause or initiation of subsequent treatment, whichever occurs first.
  • Overall survival (OS) [ Time Frame: up to month 24 post-transplant ]
    Time from the date of enrolment to the date of death due to any cause


Original Secondary Outcome: Same as current

Information By: German CLL Study Group

Dates:
Date Received: May 12, 2017
Date Started: June 2017
Date Completion: June 2021
Last Updated: May 12, 2017
Last Verified: May 2017