A phase 1b study of venetoclax and alvocidib in patients with relapsed/refractory acute myeloid leukemia

Research output: Contribution to journalResearch articleContributedpeer-review


  • Brian A Jonas - , University of California at Davis (Author)
  • Jing-Zhou Hou - , University of Pittsburgh Medical Center (UPMC) (Author)
  • Gail J Roboz - , New York Presbyterian Hospital (Author)
  • Caroline L Alvares - , Cardiff & Vale University Health Board (Author)
  • Deepa Jeyakumar - , University of California at Irvine (Author)
  • John R Edwards - , Indiana Blood and Marrow Transplantation (IBMT) (Author)
  • Harry P Erba - , Duke University (Author)
  • Richard J Kelly - , Leeds Teaching Hospitals NHS Trust (Author)
  • Christoph Röllig - , University Medicine (Faculty of Medicine and University Hospital), Department of internal Medicine I (Author)
  • Walter Fiedler - , University Hospital Hamburg Eppendorf (Author)
  • Deanna Brackman - , AbbVie Inc. (Author)
  • Satya R Siddani - , AbbVie Inc. (Author)
  • Brenda Chyla - , AbbVie Inc. (Author)
  • Jacqueline Hilger-Rolfe - , AbbVie Inc. (Author)
  • Justin M Watts - , Neurology University of Miami Miller School of Medicine FL (Author)


Relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) is a genetically complex and heterogeneous disease with a poor prognosis and limited treatment options. Thus, there is an urgent need to develop therapeutic combinations to overcome drug resistance in AML. This open-label, multicenter, international, phase 1b study evaluated the safety, efficacy, and pharmacokinetics of venetoclax in combination with alvocidib in patients with R/R AML. Patients were treated with escalating doses of venetoclax (400, 600, and 800 mg QD, orally, days 1-28) and alvocidib (45 and 60 mg/m2 , intravenously, days 1-3) in 28-day cycles. The combination was found to be safe and tolerable, with no maximum tolerated dose reached. Drug-related Grade ≥3 adverse events were reported in 23 (65.7%) for venetoclax and 24 (68.6%) for alvocidib. No drug-related AEs were fatal. Gastrointestinal toxicities, including diarrhea, nausea, and vomiting were notable and frequent; otherwise, the toxicities reported were consistent with the safety profile of both agents. The response rate was modest (complete remission [CR] + incomplete CR [CRi], 11.4%; CR + CRi + partial response rate + morphologic leukemia-free state, 20%). There was no change in alvocidib pharmacokinetics with increasing doses of venetoclax. However, when venetoclax was administered with alvocidib, AUC24 and Cmax decreased by 18% and 19%, respectively. A recommended phase 2 dose was not established due to lack of meaningful increase in efficacy across all cohorts compared to what was previously observed with each agent alone. Future studies could consider the role of the sequence, dosing, and the use of a more selective MCL1 inhibitor for the R/R AML population.


Original languageEnglish
Pages (from-to)743-752
Number of pages10
JournalHematological oncology
Issue number4
Publication statusPublished - Oct 2023

External IDs

PubMedCentral PMC10757832
Scopus 85153531933


Sustainable Development Goals


  • Humans, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bridged Bicyclo Compounds, Heterocyclic/therapeutic use, Leukemia, Myeloid, Acute/drug therapy