Phase II clinical trial of pazopanib in patients with acute myeloid leukemia (AML), relapsed or refractory or at initial diagnosis without an intensive treatment option (PazoAML)

Ann Hematol. 2019 Jun;98(6):1393-1401. doi: 10.1007/s00277-019-03651-9. Epub 2019 Mar 21.

Abstract

We evaluated pazopanib (800 mg orally QD) in patients not eligible for intensive treatment with relapsed/refractory AML or at initial diagnosis. Patients receiving pazopanib for > 14 days were analyzed for safety, tolerability, and efficacy. Co-primary endpoints were cumulative response rate and reduction of bone marrow microvessel density. Twenty patients (median age 76 years, range 52-86) were treated. Fifteen had relapsed/refractory and five had newly diagnosed AML. Median ECOG performance status was 1 (range 1-3). Four patients had adverse, 15 intermediate, and 1 patient favorable cytogenetic/molecular risk (ELN 2010 criteria). The safety profile of pazopanib was as reported. The most common adverse events of any grade were gastrointestinal. Two patients achieved PR (blast reduction > 50%), 14 stable disease (SD), and 4 progressive disease. Median PFS was 65 days (95% CI 29-105). After the end of the study, 1 CRi and 1 CRp occurred on demethylating agents, and 1 CR upon alloSCT. In these patients, SD and improved general condition on pazopanib allowed therapy escalation. Median OS for the overall study population was 191 days (95% CI 87-435) and 1-year survival was 35%. There was no significant change in microvessel density. Clinical trial information: NCT01361334.

Keywords: AML; Acute myeloid leukemia; Pazopanib; Phase II study.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow / blood supply
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Indazoles
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Microvessels / drug effects
  • Middle Aged
  • Progression-Free Survival
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Recurrence
  • Salvage Therapy
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Tumor Microenvironment / drug effects

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Indazoles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • pazopanib

Associated data

  • ClinicalTrials.gov/NCT01361334