Ibrutinib for the Treatment of AIHA in Patients With CLL/SLL or CLL-like MBL

This is a multicenter, phase II study to assess the efficacy of ibrutinib for the treatment of AIHA in adult patients with CLL/SLL or CLL-like MBL.

Patients will receive ibrutinib 420 mg/day PO for up to 12 cycles of 28 days in the absence of CLL progression or unacceptable toxicity. Every patient will be followed-up for 1 year after the completion of study treatment.

Inclusion criteria

• Diagnosis of CLL/small lymphocytic lymphoma (SLL) or CLL-like monoclonal B-cell lymphocytosis (MBL) according to IWCLL guidelines.
• Patients >18 years old
• Active AIHA (wAIHA or CAD) that i) is relapsed after previous treatment with corticosteroids (with or without rituximab), or ii) is steroid-resistant (failure to obtain hematologic response within 3 weeks on at least 1 mg/kg predniso(lo)ne), or iii) is steroid-dependent (need to continue on predniso(lo)ne at a dose of >10 mg/day to maintain a response). AIHA is defined as: anemia (hemoglobin ≤10 g/dL; or hemoglobin >10 g/dL dependent on transfusions to maintain this level of hemoglobin) and laboratory evidence of hemolysis (presence of 3 of 4 markers: increased reticulocyte count, increased indirect bilirubin, increased lactate dehydrogenase, decreased haptoglobin) and positive DAT (either IgG DAT, C3 DAT or both).
• Eligibility of patients with DAT-negative active AIHA should be confirmed by the Principal Investigator and co-Principal Investigator for the trial.
• Signed written informed consent according to ICH/EU/GCP and national local laws.

Exclusion criteria

• Contraindication to ibrutinib therapy as per treating physician's discretion.
• Contraindication to ibrutinib therapy as per ibrutinib data sheet (severe hepatic impairment, known allergy to the drug or to one of the excipients, concomitant treatment with warfarin or other vitamin K antagonists).
• Previous exposure to ibrutinib as CLL-directed therapy.
• Other CLL/SLL- or AIHA-directed treatment at the time of enrollment in the study, other than corticosteroids.
• Female patients who are currently in pregnancy or are willing to be pregnant or are lactating.