This Primary objective is evaluating the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B) for the treatment of previously untreated chronic lymphocytic leukemia (CLL). Secondary objectives: 1) To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) based on IRC assessment of PFS per IWCLL 2008 criteria.

2)To compare obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib plus obinutuzumab (Arm B) and obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) in terms of: IRC-assessed objective response rate (ORR); Tine to next treatment (TTNT); Overall Survival (OS)

This research study is evaluating the combination of three drugs - acalabrutinib, venetoclax, and obinutuzumab -- as a possible treatment for chronic lymphocytic leukemia (CLL).

The drugs involved in this study are:

* Acalabrutinib
* Venetoclax
* Obinutuzmab

Este artículo no tiene resumen

Acalabrutinib has demonstrated significant efficacy and safety in relapsed chronic lymphocytic leukemia (CLL). Efficacy and safety of acalabrutinib monotherapy were evaluated in a treatment-naive CLL cohort of a single-arm phase 1/2 trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was declined or deemed inappropriate due to comorbidities (N = 99). Patients had a median age of 64 years and 47% had Rai stage III/IV disease. Acalabrutinib was administered orally 200 mg once daily, or 100 mg twice daily until progression or intolerance. A total of 99 patients were treated; 57 (62%) had unmutated immunoglobulin heavy-chain variable gene, and 12 (18%) had TP53 aberrations. After median follow-up of 53 months, 85 patients remain on treatment; 14 discontinued treatment, mostly because of adverse events (AEs) (n = 6) or disease progression (n = 3). Overall response rate was 97% (90% partial response; 7% complete response), with similar outcomes among all prognostic subgroups. Because of improved trough BTK occupancy with twice-daily dosing, all patients were transitioned to 100 mg twice daily. Median duration of response (DOR) was not reached; 48-month DOR rate was 97% (95% confidence interval, 90-99). Serious AEs were reported in 38 patients (38%). AEs required discontinuation in 6 patients (6%) because of second primary cancers (n = 4) and infection (n = 2). Grade ≥3 events of special interest included infection (15%), hypertension (11%), bleeding events (3%), and atrial fibrillation (2%). Durable efficacy and long-term safety of acalabrutinib in this trial support its use in clinical management of symptomatic, untreated patients with CLL.

This is a multicenter non-interventional study (NIS) on patients with CLL who have been treated with acalabrutinib for the first time within the year before the first site initiation visit in Spain

Background: Bruton tyrosine kinase (BTK) is a clinically validated target in WM. Acalabrutinib is a highly selective, potent, covalent BTK inhibitor that we evaluated in a Phase 2 study of pts with treatment-naive (TN) or relapsed/refractory (R/R) WM. Methods: Pts with TN or R/R WM received 100 mg acalabrutinib BID (or 200 mg QD [n=6], later switched to 100 mg BID) in 28-day cycles until progressive disease (PD) or intolerance. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and PK. Results: One hundred six pts (14 TN and 92 R/R) were treated; median age was 69 y (range 39-90); 94% had ECOG PS ≤1; median serum IgM was 3615 mg/dL (range 291-9740). R/R pts had a median of 2 prior therapies (range 1-7). At a 25-mo median follow-up, 7 (50%) TN and 70 (76%) R/R pts remain on treatment. Discontinuations were primarily due to PD (TN 0 pts; R/R 9 pts), adverse events (AEs; TN 3; R/R 3), and investigator decision (TN 2; R/R 4). BTK occupancy and PK parameters were consistent with previous acalabrutinib studies. Efficacy outcomes are listed in the Table. Common AEs (any grade) were headache (39%), diarrhea (31%), contusion (29%), and dizziness (25%). Common Gr 3/4 AEs were neutropenia (16%), pneumonia (7%), anemia, increased ALT, and hyponatremia (each 5%). Atrial fibrillation occurred in 3 pts (1 Gr 3). Bleeding events occurred in 57% of pts (commonly contusion [29%] and epistaxis [13%]); 4 events were Gr 3/4: epistaxis, hematuria, dysfunctional uterine bleeding, and retinal hemorrhage. There were 5 Gr 5 events: pneumonia, glioblastoma multiforme, esophageal carcinoma, myocardial ischemia, and intracranial hematoma. Conclusions: Acalabrutinib is a highly effective treatment for WM with durable responses and limited toxicity.

This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body\'s immune system and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and obinutuzumab may help to control disease progression in CLL patients who have not received treatment for CLL.

Retention rate of acalabrutinib in a non-interventional setting. This is a prospective, multicentre, non-interventional study to collect real-world data on retention rates of CLL patients prescribed with acalabrutinib in Germany.

Context: 2Bruton tyrosine kinase (BTK) is a clinically validated target in WM. Acalabrutinib is a highly selective, potent, covalent BTK inhibitor that we evaluated in a Phase 2 study of pts with treatment-naive (TN) or relapsed/refractory (R/R) WM. Design: Pts with TN or R/R WM received 100 mg acalabrutinib BID (or 200 mg QD [n=6], later switched to 100 mg BID) in 28-day cycles until progressive disease (PD) or intolerance. Main outcome measures: The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and PK. Results: One hundred six pts (14 TN and 92 R/R) were treated; median age was 69 y (range 39-90); 94% had ECOG PS ≤1; median serum IgM was 3615 mg/dL (range 291-9740). R/R pts had a median of 2 prior therapies (range 1-7). At a 25-mo median follow-up, 7 (50%) TN and 70 (76%) R/R pts remain on treatment. Discontinuations were primarily due to PD (TN 0 pts; R/R 9 pts), adverse events (AEs; TN 3; R/R 3), and investigator decision (TN 2; R/R 4). BTK occupancy and PK parameters were consistent with previous acalabrutinib studies. ORR was 93 [66, 100]% and 94 [86,98]% in TN and R/R patients, respectively. The 24-month rate DOR, PFS and OS were TN.: 90 [47, 99]%, 90 [47, 99]% and 92 [54, 99]%; and

R/R:

84 [73, 90]%, 82 [72, 88]% and 89 [80, 94]%, respectively. Common AEs (any grade) were headache (39%), diarrhea (31%), contusion (29%), and dizziness (25%). Common Gr 3/4 AEs were neutropenia (16%), pneumonia (7%), anemia, increased ALT, and hyponatremia (each 5%). Atrial fibrillation occurred in 3 pts (1 Gr 3). Bleeding events occurred in 57% of pts (commonly contusion [29%] and epistaxis [13%]); 4 events were Gr 3/4: epistaxis, hematuria, dysfunctional uterine bleeding, and retinal hemorrhage. There were 5 Gr 5 events: pneumonia, glioblastoma multiforme, esophageal carcinoma, myocardial ischemia, and intracranial hematoma. Conclusions: Acalabrutinib is a highly effective treatment for WM with durable responses and limited toxicity. Funding source: Acerta Pharma, member of AstraZeneca Group (NCT02180724). Keywords: Waldenström macroglobulinemia, acalabrutinib, relapsed, refractory, treatment-naïve, BTK inhibitor

This research study is studying a combination of drugs as a possible treatment for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The names of the study drugs involved in this study are:

* obinutuzumab
* venetoclax
* acalabrutinib