Sequential Regimen of Bendamustine-Debulking Followed by CAL-101 and GA101-Induction and -Maintenance in CLL (CLL2-BCG)

• Status: Active, not recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The CLL2-BCG-trial is a prospective, open-label, multicenter phase-II-trial to evaluate the efficacy and safety of a sequential regimen of a debulking with bendamustine followed by an induction with GA101 (obinutuzumab) and CAL-101 (idelalisib) followed by CAL-101 and GA101-maintenance in CLL patients

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: German CLL Study Group
• Collaborators: Gilead Sciences; Hoffmann-La Roche
• Treatments: Bendamustine Hydrochloride; Idelalisib; Obinutuzumab

Criteria

Inclusion Criteria:

• documented chronic lymphocytic leukemia (CLL) requiring treatment according to International Working Group on CLL (iwCLL) criteria

• adequate hematologic function: platelets ≥ 25.000/µl, neutrophils ≥ 1.000/µl and hemoglobin ≥8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)

• adequate renal function: a creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection

• adequate liver function: total bilirubin ≤1,5x, aspartate aminotransferase (AST) / alanin aminotransferase (ALT) ≤2.5x the institutional upper limit of normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome

• negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration

• age ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2, ECOG 3 is only permitted if related to CLL

• life expectancy ≥ 6 months

• ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

• transformation of CLL (i.e. Richter's transformation, prolymphocytic leukemia)

• known central nervous system (CNS) involvement

• 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 cumulative illness rating scale (CIRS) 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)

• ongoing inflammatory bowel disease

• ongoing drug induced pneumonitis

• use of investigational agents which would interfere with the study drug ≤28 days prior to registration

• known hypersensitivity to GA101 (obinutuzumab), CAL-101 (idelalisib) or any of the excipients

• pregnant women and nursing mothers

• 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 regulatory or court order

• persons who are in dependence to the sponsor or an investigator