A prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by GA101 (obinutuzumab), acalabrutinib (ACP-196) and ABT-199 (venetoclax) in patients with relapsed/refractory CLL (CLL2-BAAG protocol) - CLL2-BAAG

niversität zu Köln0 sites46 target enrollmentAugust 21, 2018

ConditionsPatients with relapsed/refractory CLL requiring treatment 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]

DrugsGazyvaro Venclyxto (Venetoclax)

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Patients with relapsed/refractory CLL requiring treatment
Sponsor: niversität zu Köln
Enrollment: 46
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

August 21, 2018

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

niversität zu Köln

Eligibility Criteria

Inclusion Criteria

•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

Exclusion Criteria

•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