Format

Send to

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2008 Feb 15;14(4):1105-10. doi: 10.1158/1078-0432.CCR-07-4435.

Phase I clinical study of atacicept in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma.

Author information

  • 1Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA. ansell.stephen@mayo.edu

Abstract

PURPOSE:

B-lymphocyte stimulator and a proliferation-inducing ligand regulate B-cell homeostasis and immunoglobulin production and are overexpressed in B-cell malignancies. Atacicept (TACI-Ig), a recombinant fusion protein that inhibits both B-lymphocyte stimulator and a proliferation-inducing ligand, may be a novel treatment for B-cell malignancies.

EXPERIMENTAL DESIGN:

A phase 1, open-label, dose-escalation study of atacicept in patients with relapsed or refractory B-cell lymphoma was done. Atacicept was given s.c. weekly for 5 weeks to sequential patient cohorts at doses of 2, 4, 7, or 10 mg/kg. Patients responding or with stable disease were eligible for treatment on an extension study for up to 24 weeks or until disease progression.

RESULTS:

All patients were heavily pretreated (median number of previous treatments, 5; range, 1-10), and four patients had previously received a stem cell transplant. Four patients were treated at the 2, 4, or 7 mg/kg dose levels, and three patients received 10 mg/kg of atacicept. Atacicept was well tolerated at all doses. Three adverse events with grade 3 severity were reported for one patient, including jaw pain, gastrointestinal hemorrhage, and sepsis; all were considered unrelated to atacicept. Pharmacokinetic results were nonlinear, and treatment with atacicept resulted in dose-dependent decreases in immunoglobulin concentrations. Two patients had stable disease at 8 weeks, entered the extension study, and received additional doses of atacicept with no safety or tolerability concerns.

CONCLUSION:

Atacicept at doses of up to 10 mg/kg was well tolerated and showed biological activity by decreasing immunoglobulin concentrations, although tumor responses were not observed.

PMID:
18281543
DOI:
10.1158/1078-0432.CCR-07-4435
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center