DCLLSG

 

CLLTX1 Trial

Title Obinutuzumab containing conditioning regimen for CLL patients and patients with Richter`s transformation requiring an allogeneic stem cell transplantation
Protocol IDs EudraCT: 2015-000568-32
NCT03153514
Status prematurely terminated due to poor accrual;
completed
Contact Medical Management: Dr. Natali Pflug

Dr. Natali Pflug
+49 221 478-88220 (Office)
natali.pflug@uk-koeln.de

Project Management: Aline Zey

Aline Zey
+49 221 478-96577
aline.zey@uk-koeln.de

Data Management: Henrik Gerwin

Henrik Gerwin
+49 221 478-88177
henrik.gerwin@uk-koeln.de

Safety Management: Sabine Frohs

Sabine Frohs
+49 221 478-89621
sabine.frohs@uk-koeln.de

Contact for scientific queries Dr. Natali Pflug

Dr. Natali Pflug
+49 221 478-88220 (Office)
natali.pflug@uk-koeln.de

Design Prospective, open-label, multicentre, single-arm, phase-II trial
Objective Evaluation of 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
Key Efficacy Endpoint For this study there will be no formal primary endpoint which is connected to sample size calculation and confirmatory testing. According to the main study objective, the following key efficacy endpoint will be considered:
• Rate of patients free from disease progression (PD-free rate) at 12 months post-transplant
Additional Endpoints Other efficacy endpoints:
• MRD negativity rate at different time points (days +60, +90, +180, +270 and months 12, 18 and 24 post transplant)
• Overall response rate (ORR) following treatment at 6 months post-transplant
• Progression-free survival (PFS)
• Event-free survival (EFS)
• Overall survival (OS)
• Chimerism at day 100 post-transplant
Safety endpoints:
• Non relapse mortality (NRM) and relapse related mortality
• Engraftment post-transplant defined as > 0.50 x 109/L Neutrophils and Platelets > 20 x 109/L without transfusion requirement at 30 days post-transplant
• Incidences of grade III/IV adverse drug reactions
• Incidence and severity of acute GvHD at 100 and 365 days post transplant
• Incidence and severity of chronic GvHD within the first year post transplant
Health-related quality of life by EORTC QLQ-C30 questionnaire
Explorative endpoints
• Correlation between MRD and PFS
• Evaluation of relationship between various baseline markers and clinical outcome parameters
Study Population CLL requiring treatment according to the IWCLL guidelines

Cohort 1: Patients with poor risk CLL requiring transplant (Dreger et al., Blood 2014):
• non-response or early relapse within 24 months after purine analogue combination therapy plus high risk CLL TP53 deletion/mutation (del 17p-) and/or del 11 plus response to kinase inhibitors or other small molecules or
• non-response or early relapse within 24 months after purine analogue combination therapy and refractory to or non-tolerating kinase inhibitors or other small molecules

Cohort 2: Patients with Richter`s transformation (RT)

The CLL patients should have at least one therapy with the newer targeted agents such as BCL-2 inhibitors or BCR targeting agents.
Availability of a suitable fully matched (10/10) sibling or unrelated donor
Age  ≥ 18 to ≤ 70 years
ECOG performance status ≤ 1
Treatment Obinutuzumab i.v.
Cycle 1 in the peri-transplant and transplantation phase:
100 mg (d -8), 900 mg (d -7), 1000 mg (d -1, +7, +14)
Cycle 2 if active disease and/or MRD positivity on day +60, +90, +180 or +270: 1000 mg (d +1, +8, +15, +22)
Enrollment 3 patients
Time schedule Recruitment period: 13 November 2017 - 23 April 2018
End of study: September 2019
Clinical Study Report / Publication: Sep 2020
End of archiving period: Sep 2029
Protocol Version Protocol (Version 3.0 | 13 March 2017)
Sponsor University of Cologne
Principal Investigator Prof. Dr. Dr. M. von Bergwelt, Department I of Internal Medicine, University Hospital of Cologne
Coordinating Physician Dr. Natali Pflug, Department I of Internal Medicine, University Hospital of Cologne
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