Evaluation of a treatment with bendamustine, followed by obinutuzumab, acalabrutinib and venetoclax in patients with relapsed chronic lymphocytic leukemia
- Conditions
- Patients with 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
- EUCTR2017-003133-28-DE
- Lead Sponsor
- niversität zu Köln
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 46
1. Relapsed/refractory CLL in need of treatment according to iwCLL criteria
In case of a recent previous treatment, patients 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-BAAG trial:
- chemotherapy = 28 days
- antibody treatment = 14 days
- kinase inhibitors, BCL2-antagonists or immunomodulatory agents = 3 days
- corticosteroids may be applied until the start of the BAAG-regimen, these have to be reduced to an equivalent of = 20mg prednisolone per day during treatment
Please note: Patients with a progression during previous treatment with venetoclax, ibrutinib or another BTK inhibi-tor, as well as patients with a known resistance mutation (e.g. BTK-/PLCg2) are excluded from study participation. However, patients who progressed after termination of treatment with venetoclax, ibrutinib, other BTK inhibitors and/or obinutuzumab or who stopped treatment due to in-tolerance to ibrutinib are eligible for participation.
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 neutro-phil count = 1.0 x 109/L, a hemoglobin value =8.0 g/dL and a platelet count = 25 x 109/L, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration), in this case, platelet count should be = 10 × 109/L.
4. Adequate liver function as indicated by a total bilirubin =2x, AST/ALT =2.5x the institutional ULN value, unless di-rectly attributable to the patient’s CLL or to Gilbert’s Syn-drome
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 4 weeks until one year after last dosage of GA101 (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
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 46
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46
1. (Suspicion of) transformation of CLL (i.e. Richter’s trans-formation, pro-lymphocytic leukemia) or central nervous system (CNS) involvement
2. Progression during previous treatment with venetoclax, ibrutinib or another BTK inhibitor, and/or presence of known mutations associated with resistance to therapy, e.g. Bruton´s Tyrosine Kinase and Phospholipase C Gamma 2 (PLCg2)
3. Confirmed progressive multifocal leukoencephalopathy (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, exclud-ing 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. Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diathe-sis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure = 4 weeks or stroke/intracranial hem-orrhage = 6 months.
8. Requirement of therapy with strong CYP3A4 inhibi-tors/inducers or anticoagulant with phenprocoumon (mar-cumar) or other vitamin K-antagonists
9. Use of investigational agents = 28 days prior to start of study treatment, however, kinase inhibitors, BCL2-antagonists and antibody treatment are allowed in ac-cordance with inclusion criterion number 1 (see above).
10. Known hypersensitivity to obinutuzumab (GA101), venetoclax (ABT-199), acalabrutinib (ACP-196) 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 preg-nancy 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:
- 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