A prospective, open-label, multicenter phase-II-trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by GA101 (obinutuzumab) and CAL-101 (idelalisib) followed by CAL-101 and GA101 maintenance in CLL patients (CLL2-BCG-trial of the GCLLSG)
- Conditions
- Fit and unfit patients with relapsed/refractory CLL requiring Treatment (including relapsed/refractory patients enrolled before the second amendment and relapsed high-risk patients recruited after the second amend-ment).MedDRA 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
- EUCTR2014-000582-47-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. relapsed/refractory CLL requiring treatment according to iwCLL criteria with at least one of the following features:
-del(17p)/TP53 mutation
-ineligibility for ibrutinib due to refractoriness, intolerance or contraindications to receive ibrutinib (e.g. intake of vitamin k antagonists)
Patients must have recovered from acute toxicities of the previous treatment and pre-treatment must be stopped within the following time periods before start of the study treatment in the CLL2-BCG trial:
- chemotherapy within = 28 days
- antibody treatment within = 14 days
- kinase inhibitors, Bcl-2-antagonists or immunmodulatory agents within = 3 days
- corticosteroids may be applied until the start of the BCG-regimen, these have to be reduced to an equivalent of = 20 mg prednisolone during treatment
2. 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)
3. 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 hrs urine collection
4. Adequate liver function as indicated by a total bilirubin = 1.5x, 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 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 GA101), negative testing for hepatitis-C RNA and negative HIV antibody 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
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 therapy
5. Active 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 gastrointestinal tract)
7. Ongoing inflammatory bowel disease
8. Ongoing drug induced pneumonitis
9. Use of investigational agents which would interfere with the study drug within 28 days prior to registration
10. Known hypersensitivity to GA101 (obinutuzumab), CAL-101 (idelalisib) 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
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 (3-monthly))
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 = 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method