Study on Acalabrutinib for Treating Chronic Lymphocytic Leukemia, Richter's Syndrome, or Prolymphocytic Leukemia

Inclusion Criteria

• Adults aged 18 or older with a confirmed diagnosis of CLL/SLL that has returned or not responded after at least two previous treatments.
• Must have at least one lymph node that is 2 cm or larger.
• Active disease that meets specific criteria, such as worsening anemia, large or growing spleen or lymph nodes, or rapid increase in lymphocyte count.
• Symptoms like significant weight loss, fever, or night sweats without infection.
• Good overall health with an ECOG performance status of 0 to 2.
• Agree to use effective birth control during the study and for two days after the last dose if able to have children.
• Willing to participate in all study procedures and able to swallow capsules.
• Understand the study and provide informed consent.

Additional Criteria for Specific Groups:

• Treatment Naive: Adults with CLL/SLL who need treatment but cannot or do not want to receive chemoimmunotherapy.
• Ibrutinib Intolerant: Adults with CLL/SLL who cannot tolerate ibrutinib due to side effects.
• Richter's Syndrome/Prolymphocytic Leukemia: Adults with biopsy-proven diffuse large B cell lymphoma or prolymphocytic leukemia transformation.
• Ibrutinib Relapsed/Refractory: Adults with CLL/SLL who did not respond well to ibrutinib or whose disease has progressed after initial response.

Exclusion Criteria

• Previous cancer, except for certain skin cancers or cervical cancer, unless disease-free for at least two years.
• Serious medical conditions that could affect safety or drug absorption.
• Significant heart disease or recent heart attack.
• Digestive issues affecting drug absorption or recent stomach surgery.
• Recent immunotherapy or chemotherapy.
• Previous treatment with a BTK inhibitor, except for specific groups.
• Central nervous system involvement by lymphoma.
• Ongoing side effects from previous cancer treatments.
• Active infections like HIV, hepatitis B, or hepatitis C.
• Uncontrolled autoimmune blood disorders.
• Recent stroke or brain bleeding.
• Need for certain medications like proton-pump inhibitors or warfarin.
• Recent major surgery.
• Low blood cell counts unless due to bone marrow involvement.
• Abnormal liver or pancreas enzyme levels.
• Significant heart rhythm issues or high cardiac troponin levels.
• Pregnant or breastfeeding women.
• History of bleeding disorders.
• Participation in another clinical trial.
• Poor kidney function.
• Recent gastrointestinal ulcer.