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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Obinutuzumab i.v. \[Day 0 = day of stem cell transplant\] Cycle 1: 100 mg (d -8), 900 mg (d -7), 1000 mg (d -1, +7, +14) Cycle 2: 1000 mg (d +1, +8, +15, +22)
Universitätsklinikum Bonn
Bonn, Germany
Universitätsklinikum Köln
Cologne, Germany
Universitätsklinikum Essen
Essen, Germany
Universitätsklinikum Heidelberg
Heidelberg, Germany
PD-free rate
Rate of patients free from disease progression (key efficacy endpoint)
Time frame: 12 months post-transplant
Minimal residual disease (MRD) negativity rate
Minimal residual disease negativity rate at different time points
Time frame: days +60, +90, +180, +270 and months 12, 18 and 24 post-transplant
Overall response rate (ORR)
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)
Time frame: 6 months post-transplant
Progression-free survival (PFS)
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.
Time frame: up to month 24 post-transplant
Event-free survival (EFS)
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.
Time frame: up to month 24 post-transplant
Overall survival (OS)
Time from the date of enrolment to the date of death due to any cause
Time frame: up to month 24 post-transplant
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Universitätsklinikum Leipzig
Leipzig, Germany
Universitätsklinikum Magdeburg
Magdeburg, Germany
Universitätsklinikum München
München, Germany