Status:
COMPLETED
Sequential Regimen of Bendamustin-Debulking Followed by Obinutuzumab, Acalabrutinib and Venetoclax in Patients with Relapsed/refractory CLL
Lead Sponsor:
German CLL Study Group
Conditions:
Chronic Lymphoid Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
CLL2-BAAG is a prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of debulking with bendamustine followed by induction and maintenance with...
Detailed Description
In the CLL2-BAAG trial will be included a total of 46 patients with relapsed or refractory CLL in need of treatment.This trial will evaluate a debulking with two cycles bendamustine (only for patients...
Eligibility Criteria
Inclusion
- Relapsed/refractory CLL in need of treatment according to iwCLL (international workshop on CLL) 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 immuno-modulatory 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 inhibitor, 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.
- 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
- Adequate hematologic function as indicated by a neutrophil 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.
- 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
- 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 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
- Age ≥ 18 years
- ECOG (Eastern Cooperative Oncology Group) performance status 0 - 2, ECOG 3 is only permitted if related to CLL (e.g. due to anemia or severe constitutional symptoms)
- Life expectancy ≥ 6 months
- Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other proto-col requirements
Exclusion
- (Suspicion of) transformation of CLL (i.e. Richter's trans-formation, pro-lymphocytic leukemia) or central nervous system (CNS) involvement
- Progression during previous treatment with venetoclax, ibrutinib or another BTK inhibitor, and/or presence of known mutations associated with resistance to therapy, e.g. Bru-ton´s Tyrosine Kinase and Phospholipase C Gamma 2 (PLCg2)
- Confirmed progressive multifocal leukoencephalopathy (PML)
- Malignancies other than CLL currently requiring systemic therapies
- Uncontrolled infection requiring systemic treatment
- 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 system1 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)
- Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diathesis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure ≤ 4 weeks or stroke/intracranial hemorrhage ≤ 6 months.
- Requirement of therapy with strong CYP3A4 inhibitors/inducers or anticoagulant with phenprocoumon (marcumar) or other vitamin K-antagonists
- Use of investigational agents ≤ 28 days prior to start of study treatment, however, kinase inhibitors, BCL2-antagonists and antibody treatment are allowed in accordance with inclusion criterion number 1 (see above).
- 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
- 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)
- 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.
- Vaccination with a live vaccine ≤ 28 days prior to registration
- Legal incapacity
- Prisoners or subjects who are institutionalized by regula-tory or court order
- Persons who are in dependence to the sponsor or an investigator
Key Trial Info
Start Date :
January 14 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 26 2023
Estimated Enrollment :
46 Patients enrolled
Trial Details
Trial ID
NCT03787264
Start Date
January 14 2019
End Date
September 26 2023
Last Update
December 30 2024
Active Locations (17)
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1
Universitätsklinik Köln
Cologne, Germany, 50937
2
Gemeinschaftspraxis Hämatologie Onkologie
Dresden, Germany, 1307
3
Gemeinschaftspraxis Mohm/Prange-Krex
Dresden, Germany, 1307
4
Universitatsklinik Carl Gustav Carus
Dresden, Germany, 1307