Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL
Summary
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)
Timeline
- Start
- 2015-06-26
- Primary completion
- 2019-02-08
- Completion
- 2025-09-30
Outcome
Met primary endpoint
registry p <0.0001; Hazard Ratio (HR) 0.1 (95% CI 0.06 to 0.17); Log Rank NCT02475681 ↗
paper median progression-free survival was longer with acalabrutinib-obinutuzumab and acalabrutinib monotherapy, compared with obinutuzumab-chlorambucil PMID 32305093 ↗
release “In the ELEVATE TN trial, Calquence combined with obinutuzumab and as monotherapy reduced the risk of disease progression or death by 90% and 80%, respectively” astrazeneca.com ↗
release “Updated results from the ELEVATE-TN Phase III trial showed AstraZeneca’s Calquence (acalabrutinib) maintained a statistically significant progression-free survival (PFS) benefit versus chlorambucil plus obinutuzumab” astrazeneca.com ↗
release “AstraZeneca recently announced that the Phase III ELEVATE-TN trial met its primary endpoint at interim analysis in patients with previously-untreated CLL” astrazeneca.com ↗
release “ELEVATE TN trial, showing that Calquence (acalabrutinib) combined with obinutuzumab or as monotherapy significantly improved progression-free survival” astrazeneca.com ↗
release “In the ELEVATE-TN Phase III trial, Calquence combined with obinutuzumab and as monotherapy reduced the risk of disease progression or death by 90%” astrazeneca.com ↗
Publications
- Sharman JP, Egyed M, Jurczak W, Skarbnik A, Patel K, Flinn IW, Kamdar M, Munir T, Walewska R, Hughes M, Fogliatto LM, Herishanu Y, Banerji V, Follows G, Walker P, Ghia P, Janssens A, Byrd JC, Ferrant E, Ferrajoli A, Wierda WG, Wachira CW, Suterwala BT, Miranda P, Munugalavadla V, Wun CC, Woyach JA. Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN. Blood. 2025 Sep 11;146(11):1276-1285. doi: 10.1182/blood.2024024476.
- Kittai AS, Allan JN, James D, Bridge H, Miranda M, Yong ASM, Fam F, Roos J, Shetty V, Skarbnik A, Davids MS. An indirect comparison of acalabrutinib with and without obinutuzumab vs zanubrutinib in treatment-naive CLL. Blood Adv. 2024 Jun 11;8(11):2861-2869. doi: 10.1182/bloodadvances.2023012142.
- Sharman JP, Egyed M, Jurczak W, Skarbnik A, Pagel JM, Flinn IW, Kamdar M, Munir T, Walewska R, Corbett G, Fogliatto LM, Herishanu Y, Banerji V, Coutre S, Follows G, Walker P, Karlsson K, Ghia P, Janssens A, Cymbalista F, Woyach JA, Salles G, Wierda WG, Izumi R, Munugalavadla V, Patel P, Wang MH, Wong S, Byrd JC. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020 Apr 18;395(10232):1278-1291. doi: 10.1016/S0140-6736(20)30262-2.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Acalabrutinib | Small molecule | 100 mg | Oral |
| Comparator | Chlorambucil | Other / unclassified | 0.5 mg/kg | Oral |
| Subject | Obinutuzumab | Monoclonal antibody | 1000 mg | Intravenous |