Acalabrutinib for the Treatment of Relapsed or Refractory Autoimmune Hemolytic Anemia in Patients With Chronic Lymphocytic Leukemia

Exclusion Criteria

• •Therapeutic anticancer antibodies within 3 weeks
• •Radio- or toxin-immunoconjugates within 10 weeks
• •BH3-mimetic venetoclax, PI3K inhibitors and other "targeted" therapy- within 6 half-lives
• •Ibrutinib, acalabrutinib or another BTK inhibitor within 12 months
• •Patients on stable chronic AIHA treatments are allowed provided the dose has not changed in the 4 weeks prior to enrollment
• •Allogeneic stem cell transplant within 1 year prior to day 1 of protocol therapy, or ongoing immunosuppressive therapy for chronic graft versus host disease (cGVHD)
• •Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
• •Strong CYP3A4 inducers/ inhibitors. If the patient requires a strong CYP3A inhibitor/inducer, they should not be enrolled even if it could be held for 14 days before the first dose of study drug
• •Proton pump inhibitors (but patients who switch to H2-receptor antagonists or antacids are eligible for enrollment)
• •Chronic use of corticosteroids (\> 2 weeks) in excess of prednisone 60 mg/day or its equivalent within 4 weeks prior to start of study therapy. Rescue steroids are allowed during trial
• •Vitamin K antagonists
• •Known intolerance to acalabrutinib
• •History of bleeding disorders or with active bleeding
• •Patients with suspected or confirmed progressive multifocal leukoencephalopathy (PML)
• •Patients with history of stroke or intracranial hemorrhage within 6 months
• •Inadequate recovery from adverse events related to prior therapy to grade 1 or baseline (excluding grade 2 alopecia and neuropathy)
• •Active uncontrolled infection
• •Known history of immunodeficiency virus (HIV) infection
• •* Subjects who have an undetectable or unquantifiable HIV viral load with CD4 \> 300 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
• •Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• •* Participants who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Note that intravenous immunoglobulin therapy (IVIG) administration may lead to positive anti-HBc test result
• •* Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
• •Major surgery (requiring general anesthesia) within 28 days prior to initiation of therapy
• •Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
• •History of prior malignancy except:
• •* Malignancy treated with curative intent and no known active disease present for \>= 2 years prior to initiation of therapy on current study
• •* Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
• •* Adequately treated in situ carcinomas (e.g., breast, cervical, esophageal, etc.) without evidence of disease
• •* Asymptomatic prostate cancer managed with "watch and wait" strategy
• •Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) =\< 40%
• •Psychiatric illness/social situations that would limit compliance with study requirements
• •Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
• •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics