A prospective, open-label, multicenter phase-II trial to evatuate the efficacy and safety of a sequential regimen of bendamustine followed by GA101 and ibrutinib followed by ibrutinib and GA101 maintenance in CLL patients
- Conditions
- C91.1Chronic lymphocytic leukaemia of B-cell type
- Registration Number
- DRKS00007710
- Lead Sponsor
- niversität zu Köln
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 66
1. Have documented CLL requiring treatment (irrespective if first- or relapse treatment) according to iwCLL criteria1
In case of previously treated patients, these must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods before start of the study treatment in the CLL2-BIG trial:
- chemotherapy within = 28 days
- antibody treatment within = 14 days
- kinase inhibitors, BCL2-antagonists or immunmodulatory agents within = 3 days
- corticosteroids may be applied until the start of the BIG-regimen, these have to be reduced to an equivalent of = 20mg prednisolon during treatment
2. Creatinine clearance = 30 ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24 h urine collection
3. Adequate hematologic function as indicated by a platelet count = 25 x 109/L, a neutrophil count = 1,0 x 109/L and a hemoglobin value =8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
4. Adequate liver function as indicated by a total bilirubin = 2 x, AST, and ALT = 2.5 x the institutional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome
5. Negative serological testing for hepatitis B (i.e. 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 one year after last dosage of GA101), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
6. Age at least 18 years
7. ECOG 0 – 2; ECOG 3 is only permitted if related to CLL (e.g. due to anemia or severe constitutional symptoms)
8. Life expectancy = 6 months
9. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
1. Transformation of CLL (i.e. Richter’s transformation, prolymphocytic leukemia)
2. Known central nervous system (CNS) involvement
3. Patients with a history of confirmed PML
4. Malignancies other than CLL currently requiring systemic therapies
5. Uncontrolled infection requiring systemic treatment
6. Use of investigational agents which would interfere with the study drug within 28 days prior to registration
7. Any comorbidity or organ system impairment rated with a CIRS (cumulative illness rating scale) score of 4, excluding the eyes/ears/nose/throat/larynx organ system or any other life-threatening illness, medical condition or organ system dysfunction that – in the investigator´s opinion could comprise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract)
8. Known hypersensitivity to GA101 (obinutuzumab), ibrutinib or any of the excipients
Please note:
Patients with a known hypersensitivity to bendamustine are allowed to participate but will not receive a debulking with bendamustine
9. Requirement of treatment with strong CYP3A4-inhibitors/-inducers or anticoagulant with warfarin or phenoprocoumon (marcumar)
10. History of stroke or intracranial hemorrhage within 6 months prior to registration
11. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment, on day one of every debulking and induction cycle (monthly) and on day one of every maintenance cycle (every three months))
12. Fertile men or women of childbearing potential unless:surgically sterile or = 2 years after the onset of menopause or willing to use two methods of reliable contraception including one highly effective (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after end of study treatment.
13. Vaccination with a live vaccine a minimum of 28 days prior to registration
14. Legal incapacity
15. Prisoners or subjects who are institutionalized by regulatory or court order
16. Persons who are in dependence to the sponsor or an investigator
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) at final restaging (RE) 12 weeks after the start of the last course of induction therapy
- Secondary Outcome Measures
Name Time Method