Fit and unfit patients with previously untreated or relapsed/refractory CLL requiring treatment MedDRA version: 19.1 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Bendamustine (Levact)
Product Name: Bendamustine hydrochloride
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have documented CLL requiring treatment according to iwCLL criteria 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 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 4. 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 3 months after last dosage of GA101), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration 5. Age at least 18 years 6. ECOG 0 – 2; ECOG 3 is only permitted if related to CLL (e.g. due to anaemia or severe constitutional symptoms) 7. Life expectancy = 6 months 8. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements 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 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: 1. Transformation of CLL (i.e. Richter’s transformation, prolymphocytic leukaemia) 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. Use of investigational agents which would interfere with the study drug within 28 days prior to registration 6. Active infection requiring systemic treatment 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 8. Known hypersensitivity to GA101 (obinutuzumab), ibrutinib or any of the excipients 9. Requirement of treatment with strong CYP3A4-inhibitors/-inducers or anticoagulant with warfarin or phenoprocoumon (marcumar) 10. History of stroke or intracranial haemorrhage within 6 months prior to randomization 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) 12. Fertile men or women of childbearing potential unless: a. surgically sterile or = 2 years after the onset of menopause b. 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 12 months after end of study treatment. 13. Vaccination with a live vaccine a minimum of 28 days prior to randomization 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of a regimen of two debulking cycles of bendamustine chemotherapy followed by a sequential combination therapy of GA101 (obinutuzumab) and ibrutinib for induction and maintenance therapy in CLL patients. For this, the overall response rate (ORR) at final restaging (RE) 12 weeks after start of the last cycle of induction therapy (end of induction treatment response = EOIT) will be used as primary parameter of efficacy. In the ORR all patients achieving a (clinical) complete response (CR) / complete response with incomplete recovery of the bone marrow (CRi), partial response (PR) and PR with lymphocytosis will be included. The response will be assessed according to the iwCLL criteria; Secondary Objective: Evaluate safety of bendamustine followed by GA101 + ibrutinib for induction + maintenance. Safety: by documentation of type, frequency, severity of AEs, registering relationship of AEs to study treatment. Investigate feasibility of maintenance with GA101 + ibrutinib. Response: every 3 months during/at the end of maintenance. MRD at final restaging in patients responding to induction and every 3 months in patients with (clinical) CR and every 6 months in patients with PR during maintenance. A descriptive pairwise comparison of safety and efficacy between first line and relapse/ refractory patients + between physically fit and unfit patients. Secondary endpoints: MRD, PFS, EFS, OS, duration of response in (clinical) CR/CRi or PR/PR with lymphocytosis patients, time to next CLL treatment, BRR 6 months after final restaging, ORR after debulking and after end of maintenance, in biological defined risk groups, (clinical) CR rate + relationship between baseline markers + clinical outcome ;Primary end point(s): Overall response rate (ORR);Timepoint(s) of evaluation of this end point: at final restaging (RE; 3 months after the start of l | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety parameters: Type, frequency, and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment • MRD levels (measured in peripheral blood at interim staging, final restaging and every 3 month during maintenance therapy) • Overall response rate (ORR) in biological defined risk groups • (Clinical) complete response rate • Progression-free survival (PFS) • Event-free survival 23 • Overall survival (OS) • Duration of response in patients with (clinical) CR/ Cri and PR • Time to next CLL treatment • Evaluation of relationship between various baseline markers and clinical outcome parameters ;Timepoint(s) of evaluation of this end point: ongoing evaluation during the trial | — |
Countries
Germany
Contacts
Public ContactInformation Desk
German CLL Study Group
Outcome results
None listed