A phase 1 study of vorinostat maintenance after autologous transplant in high-risk lymphoma

Leuk Lymphoma. 2015 Apr;56(4):1043-9. doi: 10.3109/10428194.2014.963073. Epub 2014 Nov 20.

Abstract

Only a minority of patients with high risk lymphoma will be cured with autologous transplant, so maintenance with vorinostat, an oral agent with activity in relapsed lymphoma, was studied starting day + 60 for 21 consecutive days followed by a week off for up to 11 cycles. Twenty-three patients with lymphoma were treated. Ten patients completed the full 11-cycle treatment plan per protocol, four patients were removed due to progressive disease and seven withdrew or were removed from the study due to toxicities. Despite Prevnar vaccine administration every 2 months for three injections, the mean antibody concentration never reached protective levels (> 0.35 μg/mL). Fatigue and functional well-being measured by Brief Fatigue Inventory and Functional Assessment of Cancer Therapy-General improved significantly from cycle 1 to cycle 7, but depression scores from the Center for Epidemiologic Studies Depression scale did not change. Given the toxicities observed, this broad-spectrum deacetylase inhibitor at this schedule is not optimal for prolonged maintenance therapy.

Trial registration: ClinicalTrials.gov NCT00561418.

Keywords: Chemotherapeutic approaches; lymphoma and Hodgkin disease; vaccines.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Child
  • Combined Modality Therapy
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Hematopoietic Stem Cell Transplantation / methods*
  • Heptavalent Pneumococcal Conjugate Vaccine / administration & dosage
  • Heptavalent Pneumococcal Conjugate Vaccine / immunology
  • Histone Deacetylase Inhibitors / adverse effects
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Hydroxamic Acids / adverse effects
  • Hydroxamic Acids / therapeutic use*
  • Lymphoma / immunology
  • Lymphoma / pathology
  • Lymphoma / therapy*
  • Lymphopenia / chemically induced
  • Middle Aged
  • Nausea / chemically induced
  • Quality of Life
  • Recurrence
  • Transplantation, Autologous
  • Treatment Outcome
  • Vaccination / methods
  • Vorinostat

Substances

  • Heptavalent Pneumococcal Conjugate Vaccine
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Vorinostat

Associated data

  • ClinicalTrials.gov/NCT00561418