Patients with poor risk CLL and Richter`s transformation requiring an allogeneic stem cell transplantation MedDRA version: 20.0 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10058728
Conditions
Interventions
Trade Name: Gazyvaro
Product Name: Obinutuzumab
Product Code: RO5072759
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for in
Sponsors
Universität Köln
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have documented CLL according to iwCLL criteria 2. a) CLL requiring transplant according to the consensus statement 2014:1 • Non-response or early relapse within 24 months after purine analogue combination therapy or treatment of similar efficacy 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 or treatment of similar efficacy and refractory to or non-tolerating kinase inhibitors or other small molecules or b) Transformation of CLL to aggressive NHL (Richter’s transformation) The CLL patients should have at least one therapy with the newer targeted agents such as BCL-2 inhibitors or BCR targeting agents. Both poor risk CLL patients and patients with Richter`s transformation should achieve the best possible response defined as disease sensitivity measured as CR, PR or SD prior to transplant with an available salvage therapy 3. Availability of a suitable fully matched (10/10) sibling or unrelated donor 4. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of = 1. 5. Hematology values within the following limits unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome 2, hypoplastic bone marrow): • Absolute neutrophil count = 1.0 x 109/L • Platelets = 50 x 109/L and more than 7 days since last transfusion 6. Adequate liver function as indicated by a total bilirubin AST, and ALT =1.5 the institutional ULN value, unless directly attributable to the patient’s CLL 7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 1 year after last dosage of obinutuzumab), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration 8. 18 years of age or older but not older then 70 years 9. Able and willing to provide written informed consent and to comply with the study protocol procedures 10. Patient agrees to inform other physicians about study participation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 11. Previous allogeneic stem cell transplant 12. Known central nervous system (CNS) involvement 13. Patients with a history of confirmed PML 14. Clinically significant cardiac disease including unstable angina, acute myocardial infarction withinsix months prior to randomization, congestive heart failure (left ventricular ejection fraction < 50%). 15. Organ dysfunction DLCO < 50%, TLC < 70%, FEV1 < 70% and or receiving supplementary oxygen, Inadequate renal function: Creatinine clearance < 50ml/min 16. Patients with active fungal infections with radiological progression despite treatment with Ambisome or active Triazole for more than a month 17. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products 18. Hypersensitivity to Obinutuzumab or to any of the excipients such as for example Mannitol 19. Participation in another experimental drug trial (including chemotherapy, antibody treatment, kinase inhibitors, BCL2-antagonists or immunmodulatory agents) with start of the conditioning regimen/first Obinutuzumab application. 20. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment) 21. Fertile men or women of childbearing potential unless: • Surgically sterile or = 2 years after the onset of menopause • Willing to use a highly effective contraceptive method (Pearl Index < 1) such as oral hormonal contraceptives, intrauterine device, sexual abstinence or barrier method of contraception in conjunction with spermicidal jelly during study treatment and for 12 months after end of study treatment. 22. Vaccination with a live vaccine a minimum of 28 days prior to randomization 23. Prisoners or patients who are institutionalized by regulatory or court order or persons who are in dependence to the sponsor or an investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the feasibility, efficacy and safety of an Obinutuzumab containing conditioning regimen for CLL patients and patients with Richter`s transformation requiring an allogeneic stem cell transplantation. ; Secondary Objective: • Rate of patients free from disease progression at 12 months post-transplant • MRD negativity rate at different time points (days +60, +90, +180, +270 and months 12, 18 and 24 post transplant) • Overall response rate following treatment at 6 months post-transplant • Progression-free survival • Event-free survival • Overall survival • Chimerism at day 100 post-transplant • Non relapse mortality 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 • Correlation between MRD and PFS • Evaluation of relationship between various baseline markers and clinical outcome parameters ; Primary end point(s): 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 Moreover the following additional endpoints will be evaluated: Other efficacy endpoints • CLL patients: MRD negativity rate at different ti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): not applicable;Timepoint(s) of evaluation of this end point: not applicable | — |
Countries
Germany
Contacts
Public ContactCLLTX1
German CLL Study Group
Outcome results
None listed