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: 21.1 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
Product Name: Bendamustine hydrochloride
Pharmaceutical Form: Concentrate and solvent for solution for infusion
Trade Name: Zydelig
Product Name: Idelalisib / CAL-101
Pharma
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objective is to evaluate the safety of a sequential regimen of two cycles of bendamustine, followed by a combination therapy of GA101 and CAL-101 followed by CAL-101 and GA101 maintenance in CLL patients.;Primary end point(s): Overall response rate (ORR) ;Timepoint(s) of evaluation of this end point: at final restaging (RE; 12 weeks after the start of last course of induction therapy);Main Objective: The primary objective of the study is to evaluate the efficacy of a sequential regimen of two cycles of bendamustine, followed by a combination therapy of GA101 and CAL-101 (idelalisib) followed by CAL-101 and GA101 maintenance in CLL patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety parameters: Type, frequency, and severity of adverse events (AE) and adverse events of special interest (AESI) and their relationship to study treatment - MRD levels (MRD negativity is defined as <1 CLL-cell in 10,000 leukocytes analyzed [0.01%], i.e. < 1E-4) measured in peripheral blood at final restaging after end of induction treatment (12 weeks after last cycle of induction treatment) in all patients responding to study treatment and every 12 weeks (= 3 months) during the maintenance phase if the patient has achieved a (clinical) CR/CRi or every 24 weeks (= 6 months) in patients with a PR (with or without lymphocytosis) - MRD level in bone marrow optionally in patients with (clinical) CR/CRi 3 months after achievement of MRD negativity in peripheral blood - Best response rate (BRR) until 6 months after RE - ORR and clinical CR/CRi rate assessed by the investigator and the GCLLSG after debulking, at the final restaging (RE, see above) (except for the ORR by investigator assessment), after end of maintenance treatment - ORR in biological defined risk groups - Progression-free survival (PFS) - Event-free survival (EFS) - Overall survival (OS) - Duration of response in patients with: (clinical) complete response (CR), (clinical) CR with incomplete recovery of the bone marrow (CRi), partial response (PR) and PR with lymphocytosis - Treatment free survival and 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