A prospective, open-label, multicentre phase-II-trial to evaluate the efficacy and safety of a sequential regimen of Bendamustine followed by GA101 (Obinutuzumab) and ABT-199 (Venetoclax) followed by ABT-199 and GA101 maintenance in CLL patients
- Conditions
- Fit and unfit patients with previously untreated or relapsed/refractory CLL requiring treatmentMedDRA version: 21.1Level: PTClassification code 10008958Term: Chronic lymphocytic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-000580-40-DE
- Lead Sponsor
- niversity of Cologne
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 62
1. Documented CLL requiring treatment (irrespective if first or relapse treatment) according to iwCLL criteria
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 study treatment in the CLL2-BAG 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 BAG-regimen, these have to be reduced to an equivalent of = 20mg prednisolone during treatment
2. Adequate renal function, as indicated by a creatinine clearance =30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection
3. Adequate hematologic function as indicated by a platelet count = 25 x 10 9/L, a neutrophil count = 1,0 x 10 9/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 =2x, AST/ALT =2.5x the institutional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome
5. Negative serological testing for hepatitis B (HBsAg nega-tive 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
6. Age = 18 years
7. ECOG 0 to 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
Inclusion criteria for extended follow-up and re-treatment (Amendment 4 and 5):
1.Patients must have participated in the CLL2-BAG trial and must have benefitted from study treatment (clinical re-lapse =6 months after discontinuation of treatment due to a MRD negative response or, completion of 24-months of maintenance treatment or toxicity)
2.Only patients with a confirmed progression of CLL who are in need of treatment according to iwCLL 2008 criteria4 are eligible for retreatment with venetoclax and obinutuzumab
Please note: Patients with a MRD conversion from nega-tive/intermediate to positive without clinical signs of pro-gression should not (yet) receive a retreatment in the trial
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
1. Transformation of CLL (i.e. Richter’s transformation, pro-lymphocytic leukemia)
2. Known central nervous system (CNS) involvement
3. Patients with confirmed PML
4. Malignancies other than CLL currently requiring systemic therapies
5. Uncontrolled infection requiring systemic treatment
6. 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 compromise 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 gastro-intestinal tract)
7. Requirement of therapy with strong CYP3A4 inhibitors/inducers or anticoagulant with warfarin, phenprocoumon (marcumar) or other vitamin K-antagonists
8. Use of investigational agents which would interfere with the study drug within 28 days prior to registration
9. Known hypersensitivity to obinutuzumab, venetoclax 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
10. 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))
11. 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.
12. Vaccination with a live vaccine = 28 days prior to registration
13. Legal incapacity
14. Prisoners or subjects who are institutionalized by regulatory or court order
15. Persons who are in dependence to the sponsor or an investigator
Exclusion criteria for extended follow-up and re-treatment (Amendment 4 and 5):
3.Patients who received any subsequent treatment for CLL outside the study are ineligible
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method