Table 1.
Relevant Clinical Trials of Acalabrutinib for the Treatment of Patients with CLL
| Trial | Study Design/Agents Number of Patients (on Acalabrutinib Arms) | Median Follow-Up | Results | AEs (% of Patients) |
|---|---|---|---|---|
| ACE-CL-001 Phase Ib/II NCT02029443 |
Multicenter, open-label and dose-escalation study of acalabrutinib 134 RR |
41 months | ORR, 94% 45-month PFS, 62% Median PFS, not reached |
Any grade Diarrhea (52%) Headache (51%) Hypertension (22%) Atrial Fibrillation (7%) Major Bleeding (5%) Grade ≥3 Neutropenia (14%) Pneumonia (11%) Hypertension (7%) |
| ACE-CL-001 Phase Ib/II NCT02029443 |
Multicenter, open-label and dose-escalation study of acalabrutinib 99 TN |
53 months | ORR, 97% Median DOR, not reached |
Grade ≥3 Infection (15%) Hypertension (11%) Bleeding events (3%) Atrial fibrillation (2%) |
| ACE-CL-001 Phase Ib/II NCT02029443 |
Multicenter, open-label and dose-escalation study of acalabrutinib (ibrutinib-Intolerant cohort) 33 RR |
19 months | ORR, 76% 24-month PFS, 75% Median PFS, not reached |
Any grade: Diarrhea (58%) Headache (39%) Cough (33%) Grade ≥3: Neutropenia (12%) Thrombocytopenia (9%) |
| ACE-CL-208 Phase II NCT02717611 |
Multicenter, open-label study of acalabrutinib in subjects who are intolerant of ibrutinib 60 RR |
19 months | ORR, 77% 21-month PFS, 76% Median PFS, not reached |
Any grade: Diarrhea (48%) Headache (40%) Contusion (35%) Dizziness (32%) |
| ACE-CL-003 Phase Ib/II NCT02296918 |
Study of acalabrutinib in combination with obinutuzumab 19 TN 26 RR |
42 months | ORR TN, 95% ORR RR, 92% 36-month PFS TN, 94% 36-month PFS RR, 88% Median PFS, not reached (TN, RR) |
Any grade: Headache (56%) Grade ≥3: Neutropenia (24%) Syncope (11%) Weight gain (9%) Hypertension (7%) |
| ASCEND ACE-CL-309 Phase III NCT02970318 |
Randomized, multicenter, open-label study of acalabrutinib vs investigator’s choice (idelalisib plus rituximab or bendamustine plus rituximab) 155 RR |
22 months | ORR, 80% ORR + PRL, 92% 18-month PFS, 82% Median PFS, not reached |
Any grade: Headache (22%) Diarrhea (21%) Neutropenia (20%) Grade ≥3: Neutropenia (17%) Anemia (12%) |
| ELEVATE-RR ACE-CL-006 Phase III NCT02477696 |
Randomized, multicenter, open-label, non-inferiority study of acalabrutinib vs ibrutinib 268 RR |
41 months | ORR, 81% Median PFS, 38.4 months |
Any grade: Diarrhea (35%) Headache (35%) Cough (29%) URI (27%) Pyrexia (23%) Hypertension (9%) Grade ≥3: Neutropenia (20%) Anemia (12%) Pneumonia (11%) Thrombocytopenia (10%) Atrial Fibrillation (5%) |
| ELEVATE-TN Phase III ACE-CL-007 NCT02475681 |
Randomized, multicenter, open-label study of obinutuzumab plus chlorambucil vs acalabrutinib plus obinutuzumab vs acalabrutinib monotherapy 179 TN (A+O) 179 TN (A) |
29.8 months | ORR A+O, 94% ORR A, 86% 24-month PFS A+O, 93% 24-month PFS A, 87% Median PFS, not reached (A+O, A) |
Any grade (A+O, A): Headache (40%, 37%) Diarrhea (39%, 35%) Neutropenia (32%, 11%) Fatigue (28%, 18%) Contusion (24%, 15%) Arthralgia (22%, 16%) Atrial Fibrillation (3%, 4%) Grade ≥3 (A+O, A): Neutropenia (30%, 10%) Thrombocytopenia (8%, 5%) Anemia (6%, 7%) |
Abbreviations: AEs, adverse events; TN, treatment-naïve; RR, relapsed/refractory; ORR, overall response rate; PFS, progression-free survival; PRL, partial response with lymphocytosis; DOR, duration of response; A+O, acalabrutinib + obinutuzumab cohort; A, acalabrutinib monotherapy cohort.