The development of drugs that block (inhibit) Bruton tyrosine kinase (BTK), such as the oral targeted agents ibrutinib (Imbruvica; Pharmacyclics) and acalabrutinib (Calquence; AstraZeneca), has revolutionized the treatment of chronic lymphocytic leukemia (CLL). The FDA approved ibrutinib, a first-generation BTK inhibitor, for use in patients with CLL in February 2014. In November 2019, the FDA approved acalabrutinib, which is a more selective second-generation BTK inhibitor, for use in patients with advanced CLL. Researchers are now exploring the role of acalabrutinib in patients with early-stage CLL who are at high risk for disease progression with the hope that this drug may be a safer and more tolerable treatment compared with ibrutinib.
A randomized phase 2 study is underway to compare the efficacy and safety of single-agent acalabrutinib versus the combination of acalabrutinib plus obinutuzumab (Gazyva; Genentech). Obinutuzumab is a CD20-directed monoclonal antibody that was approved by the FDA in November 2013 for the treatment of patients with CLL; this drug is given by intravenous infusion. At the 2019 American Society of Hematology annual meeting, researchers shared details of this ongoing phase 2 study.
Patients can enroll in this trial if they have newly diagnosed and previously untreated early-stage CLL that, according to guidelines for initiation of therapy, does not require treatment. Patients are randomly assigned to receive either acalabrutinib (100 mg orally twice daily, Arm A) or acalabrutinib combined with obinutuzumab (Arm B). Participants in Arm C are observed every 6 months for up to 2 years.
The primary goal of Arms A and B of this trial is achievement of minimal residual disease (MRD)-negative complete remission in the bone marrow after 2 years of therapy. Residual disease refers to cancer cells that remain in the body after attempts to remove the cancer have been made. Patients who achieve “MRD-negative complete response” have no cancer cells detectable by today’s testing methods. For Arm C, the observation arm, the primary end point of the study is time to first therapy. Investigators will assess progression-free survival, overall survival, and safety for all patients in the trial.
This important clinical trial is open at 3 Mayo Clinics in the United States: Rochester, MN; Jacksonville, FL; and Scottsdale, AZ. As of December 2019, 28 patients have enrolled. The trial is expected to finish enrollment in September 2020, with analysis of study findings scheduled for September 2022. Patients and families who are interested in this clinical trial for early-stage CLL can talk with their oncologists and visit www.ClinicalTrials.gov to learn more.
