Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naïve and Relapsed or Refractory Chronic Lymphocytic Leukemia.

PURPOSE: The development of highly effective targeted agents for chronic lymphocytic leukemia offers the potential for fixed-duration combinations that achieve deep remissions without cytotoxic chemotherapy. PATIENTS AND METHODS: This phase II study tested a combination regimen of obinutuzumab, ibrutinib, and venetoclax for a total of 14 cycles in both patients with treatment-naïve (n = 25) and relapsed or refractory (n = 25) chronic lymphocytic leukemia to determine the response to therapy and safety. RESULTS: The primary end point was the rate of complete remission with undetectable minimal residual disease by flow cytometry in both the blood and bone marrow 2 months after completion of treatment, which was 28% in both groups. The overall response rate at that time was 84% in treatment-naïve patients and 88% in relapsed or refractory patients. At that time, 67% of treatment-naïve patients and 50% of relapsed or refractory patients had undetectable minimal residual disease in both the blood and marrow. At a median follow-up of 24.2 months in treatment-naïve patients and 21.5 months in relapsed or refractory patients, the median progression-free and overall survival times were not yet reached, with only 1 patient experiencing progression and 1 death. Neutropenia and thrombocytopenia were the most frequent adverse events, followed by hypertension. Grade 3 or 4 neutropenia was experienced by 66% of patients, with more events in the relapsed or refractory cohort. There was only 1 episode of neutropenic fever. A favorable impact on both perceived and objective cognitive performance during treatment was observed. CONCLUSION: The combination regimen of obinutuzumab, ibrutinib, and venetoclax offers time-limited treatment that results in deep remissions and is now being studied in phase III cooperative group trials.

An individualized inpatient diabetes education and hospital transition program for poorly controlled hospitalized patients with diabetes.

OBJECTIVE: To evaluate predictors of outcomes associated with an inpatient diabetes education and discharge support program for hospitalized patients with poorly controlled diabetes (glycated hemoglobin [HbA1c]>9%). METHODS: Patients participated in individualized diabetes education conducted by a certified diabetes educator (CDE) that included an exploration of barriers and goal setting during hospitalization with telephone follow-up and communication with primary providers at discharge. Predictors of HbA1c reduction, successful follow-up, and readmission were analyzed. RESULTS: There were 82 subjects, and 48% were insulin naïve. Patients with type 2 diabetes (T2D, n = 58) had a significant decrease in HbA1c at follow-up (-2.8%, P<.0001), while those with type 1 diabetes (T1D, n = 19) did not (+0.02%, P = .96). However, after adjustment for other factors, only increasing age, higher baseline HbA1c, earlier education, and initiation of basal insulin were significant predictors of reduction in HbA1c. Higher area level income and empowerment and earlier education were significant predictors of outpatient follow-up within 30 days. While 28% were admitted for severe hyperglycemia, only 1 patient was readmitted with severe hyperglycemia. Successful phone contact was 77% and 57% with and without the support of non-CDE assistants respectively, but all outcomes were similar. CONCLUSION: The study suggests that an individualized inpatient diabetes education and transition program is associated with a significant reduction in HbA1c that is dependent on baseline HbA1c, older age, initiation of insulin, and earlier enrollment. Additional interventions are needed to ensure better continuity of care.

EEG neurofeedback for ADHD: double-blind sham-controlled randomized pilot feasibility trial.

OBJECTIVE: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. METHOD: Unmedicated 6- to 12-year-olds with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) ADHD were randomized to active NF versus sham-NF and to 2X versus 3X/week treatment frequency. Frequency switch was allowed after Treatment 24. RESULTS: In two school years, 39 participants were recruited and 34 (87%) completed all 40 treatments. Child/parent guesses about assigned treatment were no better than chance. At Treatment 24, 38% chose 2X/week and 62% chose 3X/week. Both active NF and sham yielded large pre-post improvement on parent ratings but NF no more than sham. CONCLUSION: Blinding appears to work, and sham does not prevent recruitment/retention. Treatment frequency of 3X/week seems preferred over 2X/week and was as effective. A large double-blind RCT is feasible and necessary to test specific NF effectiveness.