Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
Summary
The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL
Timeline
- Start
- 2019-02-25
- Primary completion
- 2027-04-30
- Completion
- 2027-04-30
Outcome
Met primary endpoint
paper hazard ratio for disease progression or death with acalabrutinib-venetoclax vs. chemoimmunotherapy, 0.65 [95% confidence interval {CI}, 0.49 to 0.87], P = 0.004 PMID 39976417 ↗
paper Acalabrutinib-venetoclax with or without obinutuzumab significantly prolonged progression-free survival as compared with chemoimmunotherapy in fit patients with previously untreated CLL. PMID 39976417 ↗
release “AMPLIFY Phase III trial showed AstraZeneca’s Calquence (acalabrutinib) in combination with venetoclax demonstrated a statistically significant and clinically meaningful improvement in progression-free survival” astrazeneca.com ↗
release “Results from the AMPLIFY study showed that the fixed-duration combination regimen of VENCLEXTA and acalabrutinib was superior to FCR/BR chemoimmunotherapy.” abbvie.com ↗
Publications
- Brown JR, Seymour JF, Jurczak W, Aw A, Wach M, Illes A, Tedeschi A, Owen C, Skarbnik A, Lysak D, Eom KS, Simkovic M, Pavlovsky MA, Kater AP, Eichhorst B, Miller K, Munugalavadla V, Yu T, de Borja M, Ghia P; AMPLIFY investigators; AMPLIFY Investigators. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025 Feb 20;392(8):748-762. doi: 10.1056/NEJMoa2409804. Epub 2025 Feb 5.
- Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.
- Davids MS, Lampson BL, Tyekucheva S, Wang Z, Lowney JC, Pazienza S, Montegaard J, Patterson V, Weinstock M, Crombie JL, Ng SY, Kim AI, Jacobson CA, LaCasce AS, Armand P, Arnason JE, Fisher DC, Brown JR. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1391-1402. doi: 10.1016/S1470-2045(21)00455-1. Epub 2021 Sep 14.
- Gordon MJ, Danilov AV. The evolving role of Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia. Ther Adv Hematol. 2021 Jan 30;12:2040620721989588. doi: 10.1177/2040620721989588. eCollection 2021.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Acalabrutinib | Small molecule | — | — |
| Comparator | Bendamustine | Small molecule | — | — |
| Comparator | Cyclophosphamide | Other / unclassified | — | — |
| Comparator | Fludarabine | Small molecule | — | — |
| Comparator | Obinutuzumab | Monoclonal antibody | — | — |
| Comparator | Rituximab | Monoclonal antibody | — | — |
| Subject | Venetoclax | Small molecule | — | — |