Title | Obinutuzumab containing conditioning regimen for CLL patients and patients with Richter`s transformation requiring an allogeneic stem cell transplantation |
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Protocol IDs | EudraCT: 2015-000568-32 NCT03153514 |
Status | prematurely terminated due to poor accrual; completed |
Contact | Medical Management: Dr. Natali Pflug Dr. Natali Pflug Aline Zey Henrik Gerwin Sabine Frohs |
Contact for scientific queries | Dr. Natali Pflug Dr. Natali Pflug |
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 |
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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 |
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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 |
Documents (password protected) |
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